@article{li_wang_archibong_wu_chen_hu_ci_chen_wang_wen_et al._2022, title={Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy}, volume={9}, ISSN={["2053-714X"]}, DOI={10.1093/nsr/nwab172}, abstractNote={Abstract}, number={3}, journal={NATIONAL SCIENCE REVIEW}, author={Li, Hongjun and Wang, Zejun and Archibong, Edikan and Wu, Qing and Chen, Guojun and Hu, Quanyin and Ci, Tianyuan and Chen, Zhaowei and Wang, Jinqiang and Wen, Di and et al.}, year={2022}, month={Mar} }
 @article{chen_li_bian_wang_chen_zhang_miao_wen_wang_wan_et al._2021, title={Bioorthogonal catalytic patch}, ISSN={["1748-3395"]}, DOI={10.1038/s41565-021-00910-7}, abstractNote={Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO2 nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.}, journal={NATURE NANOTECHNOLOGY}, author={Chen, Zhaowei and Li, Hongjun and Bian, Yijie and Wang, Zejun and Chen, Guojun and Zhang, Xudong and Miao, Yimin and Wen, Di and Wang, Jinqiang and Wan, Gang and et al.}, year={2021}, month={May} }
 @article{hu_li_archibong_chen_ruan_ahn_dukhovlinova_kang_wen_dotti_et al._2021, title={Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets}, ISSN={["2157-846X"]}, DOI={10.1038/s41551-021-00712-1}, abstractNote={The immunosuppressive microenvironment of solid tumours reduces the antitumour activity of chimeric antigen receptor T cells (CAR-T cells). Here, we show that the release-through the implantation of a hyaluronic acid hydrogel-of CAR-T cells targeting the human chondroitin sulfate proteoglycan 4, polymer nanoparticles encapsulating the cytokine interleukin-15 and platelets conjugated with the checkpoint inhibitor programmed death-ligand 1 into the tumour cavity of mice with a resected subcutaneous melanoma tumour inhibits the local recurrence of the tumour as well as the growth of distant tumours, through the abscopal effect. The hydrogel, which functions as a reservoir, facilitates the enhanced distribution of the CAR-T cells within the surgical bed, and the inflammatory microenvironment triggers platelet activation and the subsequent release of platelet-derived microparticles. The post-surgery local delivery of combination immunotherapy through a biocompatible hydrogel reservoir could represent a translational route for preventing the recurrence of cancers with resectable tumours.}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Hu, Quanyin and Li, Hongjun and Archibong, Edikan and Chen, Qian and Ruan, Huitong and Ahn, Sarah and Dukhovlinova, Elena and Kang, Yang and Wen, Di and Dotti, Gianpietro and et al.}, year={2021}, month={Apr} }
 @article{paul_ostermann_chen_saville_yang_gu_whitfield_ristaino_wei_2021, title={Integrated microneedle-smartphone nucleic acid amplification platform for in-field diagnosis of plant diseases}, volume={187}, ISSN={["1873-4235"]}, url={https://doi.org/10.1016/j.bios.2021.113312}, DOI={10.1016/j.bios.2021.113312}, abstractNote={We demonstrate an integrated microneedle (MN)-smartphone nucleic acid amplification platform for “sample-to-answer” diagnosis of multiplexed plant pathogens within 30 min. This portable system consists of a polymeric MN patch for rapid nucleic acid extraction within a minute and a 3D-printed smartphone imaging device for loop-mediated isothermal amplification (LAMP) reaction and detection. We expanded the extraction of the MN technology for DNA targets as in the previous study (ACS Nano, 2019, 13, 6540–6549) to more fragile RNA biomarkers, evaluated the storability of the extracted nucleic acid samples on MN surfaces, and developed a smartphone-based LAMP amplification and fluorescent reader device that can quantify four LAMP reactions on the same chip. In addition, we have found that the MN patch containing as few as a single needle tip successfully extracted enough RNA for RT-PCR or RT-LAMP analysis. Moreover, MN-extracted RNA samples remained stable on MN surfaces for up to three days. The MN-smartphone platform has been used to detect both Phytophthora infestans DNA and tomato spotted wilt virus (TSWV) RNA down to 1 pg, comparable to the results from a benchtop thermal cycler. Finally, multiplexed detection of P. infestans and TSWV through a single extraction from infected tomato leaves and amplification on the smartphone without benchtop equipment was demonstrated.}, journal={BIOSENSORS & BIOELECTRONICS}, publisher={Elsevier BV}, author={Paul, Rajesh and Ostermann, Emily and Chen, Yuting and Saville, Amanda C. and Yang, Yuming and Gu, Zhen and Whitfield, Anna E. and Ristaino, Jean B. and Wei, Qingshan}, year={2021}, month={Sep} }
 @article{sun_wang_hu_zhou_khademhosseini_gu_2020, title={CRISPR-Cas12a delivery by DNA-mediated bioresponsive editing for cholesterol regulation}, volume={6}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.aba2983}, abstractNote={A DNA-based bioresponsive nanoformulation delivers the CRISPR-Cas12a to hepatocytes for regulating serum cholesterol.}, number={21}, journal={SCIENCE ADVANCES}, author={Sun, Wujin and Wang, Jinqiang and Hu, Quanyin and Zhou, Xingwu and Khademhosseini, Ali and Gu, Zhen}, year={2020}, month={May} }
 @article{zhang_kang_wang_yan_chen_cheng_huang_gu_2020, title={Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes}, volume={32}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201907692}, abstractNote={Abstract}, number={26}, journal={ADVANCED MATERIALS}, author={Zhang, Xudong and Kang, Yang and Wang, Jinqiang and Yan, Junjie and Chen, Qian and Cheng, Hao and Huang, Peng and Gu, Zhen}, year={2020}, month={Jul} }
 @article{yu_wang_zhang_chen_mao_ye_kahkoska_buse_langer_gu_2020, title={Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs}, volume={4}, ISSN={["2157-846X"]}, DOI={10.1038/s41551-019-0508-y}, abstractNote={Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25 kg, glucose regulation lasted >20 h with patches of ~5 cm2). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose–boronate complexes that—owing to their increased negative charge—induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery. A single removable transdermal patch bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix regulates blood glucose in insulin-deficient diabetic mice and minipigs.}, number={5}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Yu, Jicheng and Wang, Jinqiang and Zhang, Yuqi and Chen, Guojun and Mao, Weiwei and Ye, Yanqi and Kahkoska, Anna R. and Buse, John B. and Langer, Robert and Gu, Zhen}, year={2020}, month={May}, pages={499–506} }
 @misc{lee_goudie_tebon_sun_luo_lee_zhang_fetah_kim_xue_et al._2020, title={Non-transdermal microneedles for advanced drug delivery}, volume={165-166}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2019.11.010}, abstractNote={Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Lee, KangJu and Goudie, Marcus J. and Tebon, Peyton and Sun, Wujin and Luo, Zhimin and Lee, Junmin and Zhang, Shiming and Fetah, Kirsten and Kim, Han-Jun and Xue, Yumeng and et al.}, year={2020}, pages={41–59} }
 @article{richter_wan_wen_zhang_yu_kang_zhu_mckinnon_gu_qiang_et al._2020, title={Targeted Delivery of Notch Inhibitor Attenuates Obesity-Induced Glucose Intolerance and Liver Fibrosis}, volume={14}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.0c01007}, abstractNote={As the prevalence of obesity-induced type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH) continue to increase, the need for pharmacologic therapies becomes urgent. However, endeavors to identify and develop novel therapeutic strategies for these chronic conditions are balanced by the need for safety, impeding clinical translation. One shared pathology of these two diseases is a maladaptive reactivation of the Notch signaling pathway in liver. Notch antagonism with γ-secretase inhibitors effectively suppresses hepatic glucose production and reduces liver fibrosis in NASH, but its extrahepatic side effects, particularly goblet cell metaplasia, limit therapeutic utility. To overcome this barrier, we developed a nanoparticle-mediated delivery system to target γ-secretase inhibitor to liver (GSI NPs). GSI NP application reduced hepatic glucose production in diet-induced obese mice and reduced hepatic fibrosis and inflammation in mice fed a NASH-provoking diet, without apparent gastrointestinal toxicity. By changing the delivery method, these results provide proof-of-concept for the repurposing of a previously intolerable medication to address unmet needs in the clinical landscape for obesity-induced T2DM and NASH.}, number={6}, journal={ACS NANO}, author={Richter, Lauren R. and Wan, Qanfen and Wen, Di and Zhang, Yuqi and Yu, Junjie and Kang, Jin Ku and Zhu, Changyu and McKinnon, Elizabeth L. and Gu, Zhen and Qiang, Li and et al.}, year={2020}, month={Jun}, pages={6878–6886} }
 @article{ruan_hu_wen_chen_chen_lu_wang_cheng_lu_gu_2019, title={A Dual-Bioresponsive Drug-Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade}, volume={31}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201806957}, abstractNote={Abstract}, number={17}, journal={ADVANCED MATERIALS}, author={Ruan, Huitong and Hu, Quanyin and Wen, Di and Chen, Qian and Chen, Guojun and Lu, Yifei and Wang, Jinqiang and Cheng, Hao and Lu, Weiyue and Gu, Zhen}, year={2019}, month={Apr} }
 @article{yang_chen_wen_chen_wang_chen_wang_zhang_zhang_hu_et al._2019, title={A Therapeutic Microneedle Patch Made from Hair-Derived Keratin for Promoting Hair Regrowth}, volume={13}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.8b09573}, abstractNote={Activating hair follicle stem cells (HFSCs) to promote hair follicle regrowth holds promise for hair loss therapy, while challenges still remain to develop a scenario that enables enhanced therapeutic efficiency and easy administration. Here we describe a detachable microneedle patch-mediated drug delivery system, mainly made from hair-derived keratin, for sustained delivery of HFSC activators. It was demonstrated that this microneedle device integrated with mesenchymal stem cell (MSC)-derived exosomes and a small molecular drug, UK5099, could enhance the treatment efficiency at a reduced dosage, leading to promoted pigmentation and hair regrowth within 6 days through two rounds of administration in a mouse model. This microneedle-based transdermal drug delivery approach shows augmented efficacy compared to the subcutaneous injection of exosomes and topical administration of UK5099.}, number={4}, journal={ACS NANO}, author={Yang, Guang and Chen, Qian and Wen, Di and Chen, Zhaowei and Wang, Jinqiang and Chen, Guojun and Wang, Zejun and Zhang, Xudong and Zhang, Yuqi and Hu, Quanyin and et al.}, year={2019}, month={Apr}, pages={4354–4360} }
 @article{wang_wang_yu_zhang_zeng_gu_2019, title={A forskolin-conjugated insulin analog targeting endogenous glucose-transporter for glucose-responsive insulin delivery}, volume={7}, ISSN={["2047-4849"]}, DOI={10.1039/c9bm01283d}, abstractNote={A new insulin analog has been obtained by modifying insulin with forskolin (designated as insulin-F), a glucose transporter (Glut) inhibitor. Insulin-F is capable of binding to Glut on the plasma membrane in a glucose-dependent manner.}, number={11}, journal={BIOMATERIALS SCIENCE}, author={Wang, Jinqiang and Wang, Zejun and Yu, Jicheng and Zhang, Yuqi and Zeng, Yi and Gu, Zhen}, year={2019}, month={Nov}, pages={4508–4513} }
 @article{wen_wang_van den driessche_chen_zhang_chen_li_soto_liu_ohashi_et al._2019, title={Adipocytes as Anticancer Drug Delivery Depot}, volume={1}, ISSN={["2590-2385"]}, DOI={10.1016/j.matt.2019.08.007}, abstractNote={Tumor-associated adipocytes promote tumor growth by providing energy and causing chronic inflammation. Here, we have exploited the lipid metabolism to engineer adipocytes that serve as a depot to deliver cancer therapeutics at the tumor site. Rumenic acid (RA), as an anticancer fatty acid, and a doxorubicin prodrug (pDox) with a reactive oxygen species (ROS)-cleavable linker, are encapsulated in adipocytes to deliver therapeutics in a tumor-specific bioresponsive manner. After intratumoral or postsurgical administration, lipolysis releases the RA and pDox that is activated by intracellular ROS-responsive conversion, subsequently promoting antitumor efficacy. Furthermore, downregulation of PD-L1 expression is observed in tumor cells, favoring the emergence of CD4+ and CD8+ T cell-mediated immune responses.}, number={5}, journal={MATTER}, author={Wen, Di and Wang, Jinqiang and Van Den Driessche, George and Chen, Qian and Zhang, Yuqi and Chen, Guojun and Li, Hongjun and Soto, Jennifer and Liu, Ming and Ohashi, Masao and et al.}, year={2019}, month={Nov}, pages={1203–1214} }
 @article{bu_yan_wang_ruan_chen_gunadhi_bell_gu_2019, title={Advances in drug delivery for post-surgical cancer treatment}, volume={219}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/J.BIOMATERIALS.2019.04.027}, DOI={10.1016/J.BIOMATERIALS.2019.04.027}, abstractNote={Surgery remains a primary modality of treatment for the majority of solid tumor malignancies. While advancements in surgical technique and instrumentation have improved the quality of life for cancer patients, local tumor recurrence and metastasis after surgery remain challenging and result in a high rate of mortality and decrease quality of life. It is therefore urgent to explore effective methods to eliminate residual microscopic disease in the surgical site and/or circulating tumor cells (CTCs) to inhibit tumor recurrence and minimize the risk of distant metastasis. Recently, advances in bioengineering technology have facilitated the development of drug delivery systems (DDSs) for the release of chemotherapy and immunotherapy agents, which could be used to enhance the effectiveness of surgical resection. In this review, we survey the rapidly evolving fields of local and systemic controlled DDSs, utilizing a variety of formulations and devices, such as implantable wafers, injectable/sprayable hydrogels, micro/nanoparticles, and cellular particles. Opportunities and challenges for the clinical translations of these delivery systems are also discussed.}, journal={Biomaterials}, publisher={Elsevier BV}, author={Bu, Lin-Lin and Yan, Junjie and Wang, Zejun and Ruan, Huitong and Chen, Qian and Gunadhi, Vivienne and Bell, R. Bryan and Gu, Zhen}, year={2019}, month={Oct}, pages={119182} }
 @misc{zhang_yu_kahkoska_wang_buse_gu_2019, title={Advances in transdermal insulin delivery}, volume={139}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2018.12.006}, abstractNote={Insulin therapy is necessary to regulate blood glucose levels for people with type 1 diabetes and commonly used in advanced type 2 diabetes. Although subcutaneous insulin administration via hypodermic injection or pump-mediated infusion is the standard route of insulin delivery, it may be associated with pain, needle phobia, and decreased adherence, as well as the risk of infection. Therefore, transdermal insulin delivery has been widely investigated as an attractive alternative to subcutaneous approaches for diabetes management in recent years. Transdermal systems designed to prevent insulin degradation and offer controlled, sustained release of insulin may be desirable for patients and lead to increased adherence and glycemic outcomes. A challenge for transdermal insulin delivery is the inefficient passive insulin absorption through the skin due to the large molecular weight of the protein drug. In this review, we focus on the different transdermal insulin delivery techniques and their respective advantages and limitations, including chemical enhancers-promoted, electrically enhanced, mechanical force-triggered, and microneedle-assisted methods.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Zhang, Yuqi and Yu, Jicheng and Kahkoska, Anna R. and Wang, Jinqiang and Buse, John B. and Gu, Zhen}, year={2019}, month={Jan}, pages={51–70} }
 @article{chen_chen_chen_shen_zhang_wang_chan_gu_2019, title={Bioresponsive Protein Complex of aPD1 and aCD47 Antibodies for Enhanced Immunotherapy}, volume={19}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.9b00584}, abstractNote={Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.}, number={8}, journal={NANO LETTERS}, author={Chen, Qian and Chen, Guojun and Chen, Jiawen and Shen, Jingjing and Zhang, Xudong and Wang, Jinqiang and Chan, Amanda and Gu, Zhen}, year={2019}, month={Aug}, pages={4879–4889} }
 @article{bu_rao_yu_chen_deng_liu_wu_meng_guo_zhao_et al._2019, title={Cancer Stem Cell-Platelet Hybrid Membrane-Coated Magnetic Nanoparticles for Enhanced Photothermal Therapy of Head and Neck Squamous Cell Carcinoma}, volume={29}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/ADFM.201807733}, DOI={10.1002/ADFM.201807733}, abstractNote={Abstract}, number={10}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Bu, Lin-Lin and Rao, Lang and Yu, Guang-Tao and Chen, Lei and Deng, Wei-Wei and Liu, Jian-Feng and Wu, Hao and Meng, Qian-Fang and Guo, Shi-Shang and Zhao, Xing-Zhong and et al.}, year={2019}, month={Jan}, pages={1807733} }
 @article{wang_yu_zhang_zhang_kahkoska_chen_wang_sun_cai_chen_et al._2019, title={Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs}, volume={5}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.aaw4357}, abstractNote={A glucose-responsive insulin-polymer complex for self-regulated insulin release has been verified in diabetic mice and minipigs.}, number={7}, journal={SCIENCE ADVANCES}, author={Wang, Jinqiang and Yu, Jicheng and Zhang, Yuqi and Zhang, Xudong and Kahkoska, Anna R. and Chen, Guojun and Wang, Zejun and Sun, Wujin and Cai, Lulu and Chen, Zhaowei and et al.}, year={2019}, month={Jul} }
 @misc{yang_lu_bomba_gu_2019, title={Cysteine-rich Proteins for Drug Delivery and Diagnosis}, volume={26}, ISSN={["1875-533X"]}, DOI={10.2174/0929867324666170920163156}, abstractNote={An emerging focus in nanomedicine is the exploration of multifunctional nanocomposite materials that integrate stimuli-responsive, therapeutic, and/or diagnostic functions. In this effort, cysteine-rich proteins have drawn considerable attention as a versatile platform due to their good biodegradability, biocompatibility, and ease of chemical modification. This review surveys cysteine-rich protein-based biomedical materials, including protein-metal nanohybrids, gold nanoparticle-protein agglomerates, protein-based nanoparticles, and hydrogels, with an emphasis on their preparation methods, especially those based on the cysteine residue-related reactions. Their applications in tumor-targeted drug delivery and diagnostics are highlighted.}, number={8}, journal={CURRENT MEDICINAL CHEMISTRY}, author={Yang, Guang and Lu, Yue and Bomba, Hunter N. and Gu, Zhen}, year={2019}, pages={1377–1388} }
 @article{ruan_hu_wen_chen_chen_lu_wang_cheng_lu_gu_2019, title={Drug Delivery: A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade (Adv. Mater. 17/2019)}, volume={31}, ISSN={0935-9648 1521-4095}, url={http://dx.doi.org/10.1002/ADMA.201970120}, DOI={10.1002/ADMA.201970120}, abstractNote={In article number 1806957, Weiyue Lu, Zhen Gu, and co-workers engineer a dual bioresponsive drug-delivery depot that can respond to the acidic pH and reactive oxygen species within the tumor microenvironment for co-delivery of anti-PD1 antibody and an epigenetic modulator. This combination therapy increases the immunogenicity of cancer cells and enhances the antitumor immune response. The pond represents the drug-delivery depot, the duckweeds represent the tumor cells; the red fish (epigenetic agent) and the black fish (aPD1 antibody) work together to eat the duckweeds, representing the tumor cells being eliminated.}, number={17}, journal={Advanced Materials}, publisher={Wiley}, author={Ruan, Huitong and Hu, Quanyin and Wen, Di and Chen, Qian and Chen, Guojun and Lu, Yifei and Wang, Jinqiang and Cheng, Hao and Lu, Weiyue and Gu, Zhen}, year={2019}, month={Apr}, pages={1970120} }
 @article{wen_chen_chen_li_cheng_gu_2019, title={Engineering Protein Delivery Depots for Cancer Immunotherapy}, volume={30}, ISSN={1043-1802 1520-4812}, url={http://dx.doi.org/10.1021/ACS.BIOCONJCHEM.9B00061}, DOI={10.1021/ACS.BIOCONJCHEM.9B00061}, abstractNote={Cancer immunotherapy that induces a tumor-specific immune response for cancer eradication has received tremendous attention. To enhance the immunotherapeutic effects, many drug delivery strategies have been developed to overcome the physiological barriers as well as to reduce toxicity. For example, intratumoral or peritumoral administration of injectable depot formulations can directly target tumor sites for immunotherapy. Compared with systemic administration of therapeutics, this strategy has minimal side effects. Such local treatment can also trigger a systemic immune response for inhibiting tumor metastasis. This Topical Review highlights the recent studies on depot-mediated delivery of protein/peptide therapeutics for cancer immunotherapy. Further opportunities and challenges in this field are also discussed.}, number={3}, journal={Bioconjugate Chemistry}, publisher={American Chemical Society (ACS)}, author={Wen, Di and Chen, Guojun and Chen, Qian and Li, Peter Y. and Cheng, Hao and Gu, Zhen}, year={2019}, month={Mar}, pages={515–524} }
 @article{yu_wei_liu_qi_wang_chen_he_he_chen_gu_2019, title={Enhanced local cancer therapy using a CA4P and CDDP co-loaded polypeptide gel depot}, volume={7}, ISSN={["2047-4849"]}, DOI={10.1039/c8bm01442f}, abstractNote={A CA4P and CDDP co-loaded polypeptide gel depot was prepared for enhanced local colon cancer treatment.}, number={3}, journal={BIOMATERIALS SCIENCE}, author={Yu, Shuangjiang and Wei, Shu and Liu, Liang and Qi, Desheng and Wang, Jiayu and Chen, Guojun and He, Wanying and He, Chaoliang and Chen, Xuesi and Gu, Zhen}, year={2019}, month={Mar}, pages={860–866} }
 @article{paul_saville_hansel_ye_ball_williams_chang_chen_gu_ristaino_et al._2019, title={Extraction of Plant DNA by Microneedle Patch for Rapid Detection of Plant Diseases}, volume={13}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/acsnano.9b00193}, DOI={10.1021/acsnano.9b00193}, abstractNote={In-field molecular diagnosis of plant diseases via nucleic acid amplification is currently limited by cumbersome protocols for extracting and isolating pathogenic DNA from plant tissues. To address this challenge, a rapid plant DNA extraction method was developed using a disposable polymeric microneedle (MN) patch. By applying MN patches on plant leaves, amplification-assay-ready DNA can be extracted within a minute from different plant species. MN-extracted DNA was used for direct polymerase chain reaction amplification of plant plastid DNA without purification. Furthermore, using this patch device, extraction of plant pathogen DNA ( Phytophthora infestans) from both laboratory-inoculated and field-infected leaf samples was performed for detection of late blight disease in tomato. MN extraction achieved 100% detection rate of late blight infections for samples after 3 days of inoculation when compared to the conventional gold standard cetyltrimethylammonium bromide (CTAB)-based DNA extraction method and 100% detection rate for all blind field samples tested. This simple, cell-lysis-free, and purification-free DNA extraction method could be a transformative approach to facilitate rapid sample preparation for molecular diagnosis of various plant diseases directly in the field.}, number={6}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Paul, Rajesh and Saville, Amanda C. and Hansel, Jeana C. and Ye, Yanqi and Ball, Carmin and Williams, Alyssa and Chang, Xinyuan and Chen, Guojun and Gu, Zhen and Ristaino, Jean B. and et al.}, year={2019}, month={Jun}, pages={6540–6549} }
 @article{wang_yu_zhang_kahkoska_wang_fang_whitelegge_li_buse_gu_2019, title={Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia}, volume={116}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1901967116}, abstractNote={Significance}, number={22}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Wang, Jinqiang and Yu, Jicheng and Zhang, Yuqi and Kahkoska, Anna R. and Wang, Zejun and Fang, Jun and Whitelegge, Julian P. and Li, Song and Buse, John B. and Gu, Zhen}, year={2019}, month={May}, pages={10744–10748} }
 @article{chen_wang_zhang_chen_hu_li_wang_wen_zhang_lu_et al._2019, title={In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment}, volume={14}, ISSN={["1748-3395"]}, DOI={10.1038/s41565-018-0319-4}, abstractNote={Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.}, number={1}, journal={NATURE NANOTECHNOLOGY}, author={Chen, Qian and Wang, Chao and Zhang, Xudong and Chen, Guojun and Hu, Quanyin and Li, Hongjun and Wang, Jinqiang and Wen, Di and Zhang, Yuqi and Lu, Yifei and et al.}, year={2019}, month={Jan}, pages={89-+} }
 @article{chen_hu_dukhovlinova_chen_ahn_wang_ogunnaike_ligler_dotti_gu_2019, title={Photothermal Therapy Promotes Tumor Infiltration and Antitumor Activity of CAR T Cells}, volume={31}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201900192}, abstractNote={Abstract}, number={23}, journal={ADVANCED MATERIALS}, author={Chen, Qian and Hu, Quanyin and Dukhovlinova, Elena and Chen, Guojun and Ahn, Sarah and Wang, Chao and Ogunnaike, Edikan A. and Ligler, Frances S. and Dotti, Gianpietro and Gu, Zhen}, year={2019}, month={Jun} }
 @article{lu_hu_jiang_gu_2019, title={Platelet for drug delivery}, volume={58}, ISSN={0958-1669}, url={http://dx.doi.org/10.1016/J.COPBIO.2018.11.010}, DOI={10.1016/J.COPBIO.2018.11.010}, abstractNote={Platelets play a vital physiological role in hemostasis, inflammation and tissue regeneration, which are associated with wound healing as well as cancer development and metastasis. These years, a variety of platelet-mediated drug delivery approaches have been developed due to their unique properties, such as quick replenishment and site-specific activation/adhesion. In this Current Opinion, focuses are put on strategies leveraging the physiological functions of platelets for the design of drug delivery systems, including platelet engineering, platelet hitchhiking, membrane coating, synthetic platelet fabrication and platelet-triggered drug release for different applications.}, journal={Current Opinion in Biotechnology}, publisher={Elsevier BV}, author={Lu, Yifei and Hu, Quanyin and Jiang, Chen and Gu, Zhen}, year={2019}, month={Aug}, pages={81–91} }
 @article{yan_zhang_liu_ye_yu_chen_wang_zhang_hu_kang_et al._2019, title={Shape-controlled synthesis of liquid metal nanodroplets for photothermal therapy}, volume={12}, ISSN={["1998-0000"]}, DOI={10.1007/s12274-018-2262-y}, number={6}, journal={NANO RESEARCH}, author={Yan, Junjie and Zhang, Xudong and Liu, Yang and Ye, Yanqi and Yu, Jicheng and Chen, Qian and Wang, Jinqiang and Zhang, Yuqi and Hu, Quanyin and Kang, Yang and et al.}, year={2019}, month={Jun}, pages={1313–1320} }
 @article{ye_wang_sun_bomba_gu_2019, title={Topical and Transdermal Nanomedicines for Cancer Therapy}, volume={5}, ISBN={["978-3-030-01773-6"]}, ISSN={["2364-1126"]}, DOI={10.1007/978-3-030-01775-0_10}, abstractNote={Topical and transdermal nanomedicine systems have attracted considerable attention in anticancer therapy. The administration route toward the skin can transport active drugs through the skin barrier and control their entrance into the blood circulation system. Agents delivered through this platform are capable of escaping the first pass of metabolism, which causes physiological degradation of the agent and systemic clearance. Apart from methodology to facilitate the delivery of drug transdermally, the formulation of nanomedicines to preserve the therapeutic’s property is also critical for overall clinical outcomes. This strategy improves the efficiency of encapsulated drugs by potentiating the targeting capability and tailoring the release kinetics toward specific tumors. This chapter summarizes the principles and the recent innovations in the field of transdermal nanomedicine together with opportunities and challenges in clinical translation. For the continued development of novel transdermal devices incorporating nanotechnology, a deeper understanding is required in rational nanoparticle design and their pharmacokinetics.}, journal={NANOTHERANOSTICS FOR CANCER APPLICATIONS}, author={Ye, Yanqi and Wang, Jinqiang and Sun, Wujin and Bomba, Hunter N. and Gu, Zhen}, year={2019}, pages={231–251} }
 @article{luo_meng_gu_wang_zhang_wang_2019, title={Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates}, volume={15}, ISSN={1613-6810 1613-6829}, url={http://dx.doi.org/10.1002/SMLL.201900030}, DOI={10.1002/SMLL.201900030}, abstractNote={Abstract}, number={15}, journal={Small}, publisher={Wiley}, author={Luo, Jing and Meng, Jingxin and Gu, Zhen and Wang, Luying and Zhang, Feilong and Wang, Shutao}, year={2019}, month={Feb}, pages={1900030} }
 @article{yu_zhang_yan_kahkoska_gu_2018, title={Advances in bioresponsive closed-loop drug delivery systems}, volume={544}, ISSN={["1873-3476"]}, DOI={10.1016/j.ijpharm.2017.11.064}, abstractNote={Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field.}, number={2}, journal={INTERNATIONAL JOURNAL OF PHARMACEUTICS}, author={Yu, Jicheng and Zhang, Yuqi and Yan, Junjie and Kahkoska, Anna R. and Gu, Zhen}, year={2018}, month={Jun}, pages={350–357} }
 @misc{cai_gu_zhong_wen_chen_he_wu_gu_2018, title={Advances in glycosylation-mediated cancer-targeted drug delivery}, volume={23}, ISSN={["1878-5832"]}, DOI={10.1016/j.drudis.2018.02.009}, abstractNote={Targeted drug delivery for cancer therapy is expected to enhance therapeutic efficacy with minimized side effects, where the ligand-receptor recognition serves as a common targeting approach. Various ligands have been reported and carbohydrates, one of the crucial structures of tumor cell membranes, have been demonstrated effective for cell-selective binding. Hence, glycosylation-mediated cancer-targeted drug nanocarriers have received increasing attention in recent years. This review surveys a variety of glycosylated drug delivery systems as well as their applications for cancer therapy. Their challenges, opportunities, and future perspectives are also discussed in the end.}, number={5}, journal={DRUG DISCOVERY TODAY}, author={Cai, Lulu and Gu, Zhipeng and Zhong, Jian and Wen, Di and Chen, Guojun and He, Lin and Wu, Jun and Gu, Zhen}, year={2018}, month={May}, pages={1126–1138} }
 @misc{yan_lu_chen_yang_gu_2018, title={Advances in liquid metals for biomedical applications}, volume={47}, ISSN={["1460-4744"]}, DOI={10.1039/c7cs00309a}, abstractNote={This tutorial review summarizes the common performances, featured properties and various state-of-the-art biomedical applications of liquid metals.}, number={8}, journal={CHEMICAL SOCIETY REVIEWS}, author={Yan, Junjie and Lu, Yue and Chen, Guojun and Yang, Min and Gu, Zhen}, year={2018}, month={Apr}, pages={2518–2533} }
 @article{hu_chen_gu_2018, title={Advances in transformable drug delivery systems}, volume={178}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2018.03.056}, abstractNote={These years, transformable drug delivery systems (DDSs), which hold the capability of changing formulation morphology and subsequent functionality at the desired disease site, have shown great promise in control of spatio-temporal drug delivery/release manner and enhanced treatment efficacy. Equipped with controllability and design flexibility, the transformable DDSs are being increasingly pursued for the development of precision drug delivery platforms for biomedical applications. In this review, we describe the recently developed intracelluarly and extracellularly transformable DDSs, especially associated with assembly or disassociation of the original formulation units, for achieving various functionalities, including prolonged retention time, inhibited endocytosis and enhanced cytotoxicity. Furthermore, the different stimuli, such as pH, enzyme, light, temperature, redox and mechanical force that trigger the transformation process are also introduced. The future outlook and challenges are discussed in the end.}, journal={BIOMATERIALS}, author={Hu, Quanyin and Chen, Qian and Gu, Zhen}, year={2018}, month={Sep}, pages={546–558} }
 @article{chen_wang_qin_zhang_zhang_sun_gu_2018, title={Bacteria-Driven Hypoxia Targeting for Combined Biotherapy and Photothermal Therapy}, volume={12}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.8b02235}, abstractNote={The facultative anaerobe Salmonella strain VNP20009 selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. However, the phase 1 clinical trial of VNP20009 has been terminated mainly due to its weak antitumor effects and exhibition of dose-dependent toxicity. Here, we leveraged the advantages of VNP20009 biotherapy together with polydopamine-mediated photothermal therapy in order to enhance the antitumor efficacy toward malignant melanoma. VNP20009 was coated with polydopamine via oxidation and self-polymerization, which was then injected into tumor-bearing mice via the tail vein. Polydopamine-coated VNP20009 targeted hypoxic areas of the solid tumors, and near-infrared laser irradiation of the tumors induced heating due to polydopamine. This combined approach eliminated the tumors without relapse or metastasis with only one injection and laser irradiation. More importantly, we found both VNP and pDA potentiate the therapeutic ability of each other, resulting in a superior anticancer effect.}, number={6}, journal={ACS NANO}, author={Chen, Wenfei and Wang, Ying and Qin, Ming and Zhang, Xudong and Zhang, Zhirong and Sun, Xun and Gu, Zhen}, year={2018}, month={Jun}, pages={5995–6005} }
 @article{luo_sun_fang_lee_li_gu_dokmeci_khademhosseini_2018, title={Biodegradable Gelatin Methacryloyl Microneedles for Transdermal Drug Delivery}, volume={8}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201801054}, DOI={10.1002/ADHM.201801054}, abstractNote={Abstract}, number={3}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Luo, Zhimin and Sun, Wujin and Fang, Jun and Lee, KangJu and Li, Song and Gu, Zhen and Dokmeci, Mehmet R. and Khademhosseini, Ali}, year={2018}, month={Dec}, pages={1801054} }
 @article{zhang_wang_yu_wen_kahkoska_lu_zhang_buse_gu_2018, title={Bioresponsive Microneedles with a Sheath Structure for H2O2 and pH Cascade-Triggered Insulin Delivery}, volume={14}, ISSN={["1613-6829"]}, DOI={10.1002/smll.201704181}, abstractNote={Abstract}, number={14}, journal={SMALL}, author={Zhang, Yuqi and Wang, Jinqiang and Yu, Jicheng and Wen, Di and Kahkoska, Anna R. and Lu, Yue and Zhang, Xudong and Buse, John B. and Gu, Zhen}, year={2018}, month={Apr} }
 @misc{xue_zhang_xu_yan_gu_kang_2018, title={Blood sampling using microneedles as a minimally invasive platform for biomedical diagnostics}, volume={13}, ISSN={["2352-9407"]}, DOI={10.1016/j.apmt.2018.08.013}, abstractNote={Blood is the most important body fluid in humans, transporting nutrients into the tissues and organs while removing metabolic wastes from cells. Regular blood tests can reveal many physiological and biochemical indexes that are critical for diagnosis of various diseases and evaluation of therapeutic efficacy. However, the traditional hypodermal blood sampling method contradicts patient compliance due to the induced pain, bleeding and the requirement of skilled professionals. For point-of-care diagnosis, blood extraction systems are desired to be easy, safe and fast for collecting essential tiny volumes of sample. Microneedles have attracted considerable attention as a novel transdermal blood extraction tool with superior advantages, including painless experience, low cost and high safety. Moreover, various sensors and actuators can be integrated into the microneedle platform for continuously monitoring bio-analytes after extracting and guiding the blood sample into the analytical unit. In this review, we highlight the characteristics of skin structures and the existing blood sampling techniques in clinics and in nature, focusing on several critical aspects of microneedle platforms for transdermal blood extraction and analysis, including materials composition, actuator fabrication, sensing methods and the future prospects toward clinical translation.}, journal={APPLIED MATERIALS TODAY}, author={Xue, Peng and Zhang, Lei and Xu, Zhigang and Yan, Junjie and Gu, Zhen and Kang, Yuejun}, year={2018}, month={Dec}, pages={144–157} }
 @article{zhang_wang_wang_hu_langworthy_ye_sun_lin_wang_fine_et al._2018, title={Cancer Immunotherapy: PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy (Adv. Mater. 22/2018)}, volume={30}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201870152}, DOI={10.1002/ADMA.201870152}, abstractNote={In article number 1707112, Peng Huang, Zhen Gu, and co-workers engineer cellular nanovesicles presenting PD-1 receptors on their membranes, which enhance antitumor response by disrupting the PD-1/PD-L1 immune inhibitory axis. These nanovesicles could also be adapted to carry a variety of therapeutics to achieve synergistic cancer therapy.}, number={22}, journal={Advanced Materials}, publisher={Wiley}, author={Zhang, Xudong and Wang, Chao and Wang, Jinqiang and Hu, Quanyin and Langworthy, Benjamin and Ye, Yanqi and Sun, Wujin and Lin, Jing and Wang, Tianfu and Fine, Jason and et al.}, year={2018}, month={May}, pages={1870152} }
 @article{tang_wang_huang_ye_su_qiao_hensley_caranasos_zhang_gu_et al._2018, title={Cardiac cell-integrated microneedle patch for treating myocardial infarction}, volume={4}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.aat9365}, DOI={10.1126/sciadv.aat9365}, abstractNote={A microneedle cardiac stromal cell patch has been developed for therapeutic heart regeneration after myocardial infarction.}, number={11}, journal={SCIENCE ADVANCES}, publisher={American Association for the Advancement of Science (AAAS)}, author={Tang, Junnan and Wang, Jinqiang and Huang, Ke and Ye, Yanqi and Su, Teng and Qiao, Li and Hensley, Michael Taylor and Caranasos, Thomas George and Zhang, Jinying and Gu, Zhen and et al.}, year={2018}, month={Nov} }
 @article{fan_li_luo_chen_wang_zhang_shen_gu_wang_2018, title={Cationic lipid-assisted nanoparticles for delivery of mRNA cancer vaccine}, volume={6}, ISSN={2047-4830 2047-4849}, url={http://dx.doi.org/10.1039/C8BM00908B}, DOI={10.1039/C8BM00908B}, abstractNote={Schematic diagram showing that CLANmRNA stimulates the maturation of DCs, promotes the expansion of antigen-specific T cells and induces robust anti-tumor immune response.}, number={11}, journal={Biomaterials Science}, publisher={Royal Society of Chemistry (RSC)}, author={Fan, Ya-Nan and Li, Min and Luo, Ying-Li and Chen, Qian and Wang, Li and Zhang, Hou-Bing and Shen, Song and Gu, Zhen and Wang, Jun}, year={2018}, pages={3009–3018} }
 @misc{wang_wen_gu_2018, title={Cellular Bioparticulates with Therapeutics for Cancer Immunotherapy}, volume={29}, ISSN={["1043-1802"]}, DOI={10.1021/acs.bioconjchem.7b00619}, abstractNote={Cancer immunotherapy has received considerable attention because of a variety of exciting clinical outcomes in recent years. At the interface of cancer immunotherapy and bioengineering, there are many opportunities to further improve the treatment efficacy or address current challenges in immunotherapy. Cellular bioparticulates as promising carriers of immunomodulators have attracted much attention due to their inherent biocompatibility and unique biological properties. This Topical Review highlights recently reported studies utilizing bioparticulates for cancer immunotherapy, including engineered red blood cells (RBC) and RBC membrane coated particles, engineered T-cells, engineered platelets, and engineered microbes.}, number={3}, journal={BIOCONJUGATE CHEMISTRY}, author={Wang, Chao and Wen, Di and Gu, Zhen}, year={2018}, month={Mar}, pages={702–708} }
 @article{hu_sun_wang_ruan_zhang_ye_shen_wang_lu_cheng_et al._2018, title={Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy}, volume={2}, ISSN={["2157-846X"]}, DOI={10.1038/s41551-018-0310-2}, abstractNote={Patients with acute myeloid leukaemia who relapse following therapy have few treatment options and face poor outcomes. Immune checkpoint inhibition, for example, by antibody-mediated programmed death-1 (PD-1) blockade, is a potent therapeutic modality that improves treatment outcomes in acute myeloid leukaemia. Here, we show that systemically delivered blood platelets decorated with anti-PD-1 antibodies (aPD-1) and conjugated to haematopoietic stem cells (HSCs) suppress the growth and recurrence of leukaemia in mice. Following intravenous injection into mice bearing leukaemia cells, the HSC-platelet-aPD-1 conjugate migrated to the bone marrow and locally released aPD-1, significantly enhancing anti-leukaemia immune responses, and increasing the number of active T cells, production of cytokines and chemokines, and survival time of the mice. This cellular conjugate also promoted resistance to re-challenge with leukaemia cells. Taking advantage of the homing capability of HSCs and in situ activation of platelets for the enhanced delivery of a checkpoint inhibitor, this cellular combination-mediated drug delivery strategy can significantly augment the therapeutic efficacy of checkpoint blockade.}, number={11}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Hu, Quanyin and Sun, Wujin and Wang, Jinqiang and Ruan, Huitong and Zhang, Xudong and Ye, Yanqi and Shen, Song and Wang, Chao and Lu, Weiyue and Cheng, Ke and et al.}, year={2018}, month={Nov}, pages={831–840} }
 @article{wang_ye_yu_kahkoska_zhang_wang_sun_corder_chen_khan_et al._2018, title={Core–Shell Microneedle Gel for Self-Regulated Insulin Delivery}, volume={12}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/ACSNANO.7B08152}, DOI={10.1021/ACSNANO.7B08152}, abstractNote={A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.}, number={3}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Wang, Jinqiang and Ye, Yanqi and Yu, Jicheng and Kahkoska, Anna R. and Zhang, Xudong and Wang, Chao and Sun, Wujin and Corder, Ria D. and Chen, Zhaowei and Khan, Saad A. and et al.}, year={2018}, month={Feb}, pages={2466–2473} }
 @article{chen_wang_chen_hu_gu_2018, title={Delivery Strategies for Immune Checkpoint Blockade}, volume={7}, ISSN={["2192-2659"]}, DOI={10.1002/adhm.201800424}, abstractNote={Abstract}, number={20}, journal={ADVANCED HEALTHCARE MATERIALS}, author={Chen, Qian and Wang, Chao and Chen, Guojun and Hu, Quanyin and Gu, Zhen}, year={2018}, month={Oct} }
 @article{ji_xiao_xu_he_qian_li_wu_chen_wang_hu_et al._2018, title={Drug-Bearing Supramolecular MMP Inhibitor Nanofibers for Inhibition of Metastasis and Growth of Liver Cancer}, volume={5}, ISSN={2198-3844}, url={http://dx.doi.org/10.1002/ADVS.201700867}, DOI={10.1002/ADVS.201700867}, abstractNote={Abstract}, number={8}, journal={Advanced Science}, publisher={Wiley}, author={Ji, Yujie and Xiao, Yanyu and Xu, Liu and He, Jiayu and Qian, Chen and Li, Weidong and Wu, Li and Chen, Rui and Wang, Jingjing and Hu, Rongfeng and et al.}, year={2018}, month={Jun}, pages={1700867} }
 @article{zhang_wang_chen_hu_wang_yan_dotti_huang_gu_2018, title={Engineering PD-1-Presenting Platelets for Cancer Immunotherapy}, volume={18}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.8b02321}, abstractNote={Radical surgery still represents the treatment choice for several malignancies. However, local and distant tumor relapses remain the major causes of treatment failure, indicating that a postsurgery consolidation treatment is necessary. Immunotherapy with checkpoint inhibitors has elicited impressive clinical responses in several types of human malignancies and may represent the ideal consolidation treatment after surgery. Here, we genetically engineered platelets from megakaryocyte (MK) progenitor cells to express the programmed cell death protein 1 (PD-1). The PD-1 platelet and its derived microparticle could accumulate within the tumor surgical wound and revert exhausted CD8+ T cells, leading to the eradication of residual tumor cells. Furthermore, when a low dose of cyclophosphamide (CP) was loaded into PD-1-expressing platelets to deplete regulatory T cells (Tregs), an increased frequency of reinvigorated CD8+ lymphocyte cells was observed within the postsurgery tumor microenvironment, directly preventing tumor relapse.}, number={9}, journal={NANO LETTERS}, author={Zhang, Xudong and Wang, Jinqiang and Chen, Zhaowei and Hu, Quanyin and Wang, Chao and Yan, Junjie and Dotti, Gianpietro and Huang, Peng and Gu, Zhen}, year={2018}, month={Sep}, pages={5716–5725} }
 @article{bakh_cortinas_weiss_langer_anderson_gu_dutta_strano_2018, title={Glucose-responsive insulin by molecular and physical design (vol 9, pg 937, 2017)}, volume={10}, ISSN={["1755-4349"]}, DOI={10.1038/nchem.2898}, abstractNote={This corrects the article DOI: 10.1038/nchem.2857.}, number={1}, journal={NATURE CHEMISTRY}, author={Bakh, Naveed A. and Cortinas, Abel B. and Weiss, Michael A. and Langer, Robert S. and Anderson, Daniel G. and Gu, Zhen and Dutta, Sanjoy and Strano, Michael S.}, year={2018}, month={Jan}, pages={109–109} }
 @article{yu_zhang_wang_wen_kahkoska_buse_gu_2018, title={Glucose-responsive oral insulin delivery for postprandial glycemic regulation}, volume={12}, ISSN={1998-0124 1998-0000}, url={http://dx.doi.org/10.1007/S12274-018-2264-9}, DOI={10.1007/S12274-018-2264-9}, abstractNote={Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications. Herein, we report a glucose-responsive oral insulin delivery system based on Fc receptor (FcRn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic regulation. After oral administration, the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive binding of glucose with the phenylboronic acid groups conjugated with HA. The exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal absorption in an FcRn-mediated transport pathway. In vivo studies on chemically-induced type 1 diabetic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial blood glucose excursions. This work is the first demonstration of an oral insulin delivery system directly triggered by increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.}, number={7}, journal={Nano Research}, publisher={Springer Science and Business Media LLC}, author={Yu, Jicheng and Zhang, Yuqi and Wang, Jinqiang and Wen, Di and Kahkoska, Anna R. and Buse, John B. and Gu, Zhen}, year={2018}, month={Dec}, pages={1539–1545} }
 @article{liu_shen_wen_li_li_chen_gu_mo_2018, title={Hierarchical Nanoassemblies-Assisted Combinational Delivery of Cytotoxic Protein and Antibiotic for Cancer Treatment}, volume={18}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.7b04976}, abstractNote={Protein therapeutics hold increasing interest with the promise of revolutionizing the cancer treatment by virtue of a potent specific activity and reduced adverse effects. Nonetheless, the therapeutic efficacy of anticancer proteins is highly compromised by multiple successive physiological barriers to protein delivery. In addition, concurrent elimination of bulk tumor cells and highly tumorigenic cancer stem-like cells (CSCs) as a promising strategy has been evidenced to significantly improve cancer therapy. Here we show that a hierarchically assembled nanocomposite can self-adaptively transform its particulate property in response to endogenous tumor-associated signals to overcome the sequential barriers and achieve an enhanced antitumor efficacy by killing CSCs and bulk tumor cells synchronously. The nanoassemblies preferentially accumulate in tumors and dissociate under tumor microenvironmental acidity accompanied by the extracellular release of small-sized ribonuclease A (RNase A)-encapsulated nanocapsule (R-rNC) and small-molecule anti-CSC doxycycline (Doc), which exhibit increased tumor penetration and intracellular accumulation. The endocytosed R-rNC rapidly releases RNase A within both CSCs and tumor cells at intracellular reductive conditions, causing cell death by catalyzing RNA degradation, while Doc eradicates CSCs by inhibiting the mitochondrial biogenesis. The hierarchical assemblies show enhanced cytotoxicity on the CSC-enriched MDA-MB-231 mammospheres and an enhanced antitumor efficacy on the xenograft tumor mouse model.}, number={4}, journal={NANO LETTERS}, author={Liu, Meng and Shen, Shiyang and Wen, Di and Li, Mengru and Li, Teng and Chen, Xiaojie and Gu, Zhen and Mo, Ran}, year={2018}, month={Apr}, pages={2294–2303} }
 @article{wang_wang_zhang_yu_wen_hu_ye_bomba_hu_liu_et al._2018, title={In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy}, volume={10}, ISSN={["1946-6242"]}, DOI={10.1126/scitranslmed.aan3682}, abstractNote={A ROS-responsive hydrogel scaffold controls release of gemcitabine and immune checkpoint inhibitor for enhanced antitumor activity.}, number={429}, journal={SCIENCE TRANSLATIONAL MEDICINE}, author={Wang, Chao and Wang, Jinqiang and Zhang, Xudong and Yu, Shuangjiang and Wen, Di and Hu, Quanyin and Ye, Yanqi and Bomba, Hunter and Hu, Xiuli and Liu, Zhuang and et al.}, year={2018}, month={Feb} }
 @article{yu_wang_yu_wang_lu_zhang_zhang_hu_sun_he_et al._2018, title={Injectable Bioresponsive Gel Depot for Enhanced Immune Checkpoint Blockade}, volume={30}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201801527}, DOI={10.1002/ADMA.201801527}, abstractNote={Abstract}, number={28}, journal={Advanced Materials}, publisher={Wiley}, author={Yu, Shuangjiang and Wang, Chao and Yu, Jicheng and Wang, Jinqiang and Lu, Yue and Zhang, Yuqi and Zhang, Xudong and Hu, Quanyin and Sun, Wujin and He, Chaoliang and et al.}, year={2018}, month={May}, pages={1801527} }
 @article{gu_2018, title={Leverage physiology for precision medications}, volume={14}, ISSN={1549-9634}, url={http://dx.doi.org/10.1016/J.NANO.2017.11.378}, DOI={10.1016/J.NANO.2017.11.378}, number={5}, journal={Nanomedicine: Nanotechnology, Biology and Medicine}, publisher={Elsevier BV}, author={Gu, Zhen}, year={2018}, month={Jul}, pages={1883–1884} }
 @misc{chen_hu_gu_2018, title={Leveraging Engineering of Cells for Drug Delivery}, volume={51}, ISSN={["1520-4898"]}, DOI={10.1021/acs.accounts.7b00526}, abstractNote={Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns. As a recent emerging research topic, drawing inspiration from the ways that natural cells interact with the body has opened new avenues for cell engineering, such as direct modification of whole cells with synthetic materials and "top-down" integration of biological membranes with micro/nanomaterials, which aim to alleviate immune response while harnessing the complex biological functions of cells. In this Account, we summarize our recent contribution to the field of cell engineering methodologies, with which we have demonstrated their promising applications for cancer immunotherapy, targeted drug delivery, and blood glucose regulation. For example, inspired by the inherent ability of platelets to accumulate at wound sites and interact with circulating tumor cells, we exploited a targeted checkpoint antibody delivery strategy for treatment of postsurgical cancer recurrence and metastatic spread by covalent binding of platelets' cell surfaces with a monoclonal antibody against programmed-death ligand 1 (aPDL1). Without interfering with the platelets' surgical-site homing property, the conjugated aPDL1 could be triggered to release in the form of microparticles after in situ activation. As an extension, we then engineered the platelet membrane to cloak nanoparticles for anticancer drug delivery, mimicking the targeting capability of the source cells while possessing prolonged circulation lifetime and insignificant immunogenicity. At the same time, we also found that the subcellular compartment membrane-derived particulates exhibited high specificity toward homotypic cells, by which enhanced intracellular drug delivery was achieved. Moreover, by taking advantage of the reversible interaction between glucose-derivative-modified insulin and the red blood cell membrane, we constructed a glucose-responsive smart insulin delivery system for long-term maintenance of blood glucose levels within a normal range. Recently, by virtue of painless microneedle patches as convenient cell engineering platforms, a minimally invasive intradermal antitumor vaccine was invented by integrating whole-tumor lysis into near-infrared light-illuminated microneedle patches. The microneedle patches also showed promise in combining with conventional cell encapsulation techniques, by which an externally positioned β-cell engineering strategy was proposed for diabetes treatment. The results presented in this Account demonstrate distinct approaches to the development and application of cell engineering strategies for drug delivery.}, number={3}, journal={ACCOUNTS OF CHEMICAL RESEARCH}, author={Chen, Zhaowei and Hu, Quanyin and Gu, Zhen}, year={2018}, month={Mar}, pages={668–677} }
 @article{zhao_jin_chen_yang_chen_meng_lu_gu_he_2018, title={Local generation of hydrogen for enhanced photothermal therapy}, volume={9}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/S41467-018-06630-2}, DOI={10.1038/S41467-018-06630-2}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Zhao, Penghe and Jin, Zhaokui and Chen, Qian and Yang, Tian and Chen, Danyang and Meng, Jin and Lu, Xifeng and Gu, Zhen and He, Qianjun}, year={2018}, month={Oct} }
 @article{luo_xu_li_cao_liu_wang_du_yang_gu_wang_2018, title={Macrophage-Specific in Vivo Gene Editing Using Cationic Lipid-Assisted Polymeric Nanoparticles}, volume={12}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.7b07874}, abstractNote={The CRISPR/Cas9 gene editing technology holds promise for the treatment of multiple diseases. However, the inability to perform specific gene editing in targeted tissues and cells, which may cause off-target effects, is one of the critical bottlenecks for therapeutic application of CRISPR/Cas9. Herein, macrophage-specific promoter-driven Cas9 expression plasmids (pM458 and pM330) were constructed and encapsulated in cationic lipid-assisted PEG-b-PLGA nanoparticles (CLAN). The obtained nanoparticles encapsulating the CRISPR/Cas9 plasmids were able to specifically express Cas9 in macrophages as well as their precursor monocytes both in vitro and in vivo. More importantly, after further encoding a guide RNA targeting Ntn1 (sgNtn1) into the plasmid, the resultant CLANpM330/sgNtn1 successfully disrupted the Ntn1 gene in macrophages and their precursor monocytes in vivo, which reduced expression of netrin-1 (encoded by Ntn1) and subsequently improved type 2 diabetes (T2D) symptoms. Meanwhile, the Ntn1 gene was not disrupted in other cells due to specific expression of Cas9 by the CD68 promoter. This strategy provides alternative avenues for specific in vivo gene editing with the CRISPR/Cas9 system.}, number={2}, journal={ACS NANO}, author={Luo, Ying-Li and Xu, Cong-Fei and Li, Hong-Jun and Cao, Zhi-Ting and Liu, Jing and Wang, Ji-Long and Du, Xiao-Jiao and Yang, Xian-Zhu and Gu, Zhen and Wang, Jun}, year={2018}, month={Feb}, pages={994–1005} }
 @article{zhang_yu_qiang_gu_2018, title={Nanomedicine for obesity treatment}, volume={61}, ISSN={1674-7305 1869-1889}, url={http://dx.doi.org/10.1007/S11427-017-9257-1}, DOI={10.1007/S11427-017-9257-1}, abstractNote={Obesity, as a chronic condition, has been a serious public health issue over the last decades both in the affluent Western world and developing countries. As reported, the risk of several serious diseases increases with weight gain, including type 2 diabetes, coronary heart disease, cancer, and respiratory diseases. In addition to lifestyle modifications, pharmacotherapy has become an important strategy to control weight gain. However, most of the anti-obesity drugs often show poor outcome for weight-loss and cause severe adverse effects. This review surveys recent advances in nanomedicine as an emerging strategy for obesity treatment with an emphasis on the enhanced therapeutic efficiency and minimized side effects. The insights for future development are also discussed.}, number={4}, journal={Science China Life Sciences}, publisher={Springer Science and Business Media LLC}, author={Zhang, Yuqi and Yu, Jicheng and Qiang, Li and Gu, Zhen}, year={2018}, month={Mar}, pages={373–379} }
 @article{zhang_wang_wang_hu_langworthy_ye_sun_lin_wang_fine_et al._2018, title={PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy}, volume={30}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201707112}, abstractNote={Abstract}, number={22}, journal={ADVANCED MATERIALS}, author={Zhang, Xudong and Wang, Chao and Wang, Jinqiang and Hu, Quanyin and Langworthy, Benjamin and Ye, Yanqi and Sun, Wujin and Lin, Jing and Wang, Tianfu and Fine, Jason and et al.}, year={2018}, month={May} }
 @article{wu_cai_zhu_li_shi_su_yue_gu_2018, title={PDT-Driven Highly Efficient Intracellular Delivery and Controlled Release of CO in Combination with Sufficient Singlet Oxygen Production for Synergistic Anticancer Therapy}, volume={28}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/ADFM.201804324}, DOI={10.1002/ADFM.201804324}, abstractNote={Abstract}, number={41}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Wu, Lihuang and Cai, Xiaojun and Zhu, Haofang and Li, Junhua and Shi, Dongxu and Su, Dunfan and Yue, Dong and Gu, Zhongwei}, year={2018}, month={Aug}, pages={1804324} }
 @misc{ye_yu_wen_kahkoska_gu_2018, title={Polymeric microneedles for transdermal protein delivery}, volume={127}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2018.01.015}, abstractNote={The intrinsic properties of therapeutic proteins generally present a major impediment for transdermal delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal protein delivery. The clinical potential and future translation of MNs are also discussed.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Ye, Yanqi and Yu, Jicheng and Wen, Di and Kahkoska, Anna R. and Gu, Zhen}, year={2018}, month={Mar}, pages={106–118} }
 @article{zhang_feng_yu_yang_zhao_wang_shen_gu_2018, title={ROS-Responsive Microneedle Patch for Acne Vulgaris Treatment}, volume={1}, ISSN={2366-3987}, url={http://dx.doi.org/10.1002/ADTP.201800035}, DOI={10.1002/ADTP.201800035}, abstractNote={Abstract}, number={3}, journal={Advanced Therapeutics}, publisher={Wiley}, author={Zhang, Yuqi and Feng, Peijian and Yu, Jicheng and Yang, Jia and Zhao, Jiacheng and Wang, Jinqiang and Shen, Qundong and Gu, Zhen}, year={2018}, month={May}, pages={1800035} }
 @article{zhang_feng_yu_yang_zhao_wang_shen_gu_2018, title={ROS-Responsive Microneedle Patch for Acne Vulgaris Treatment (Adv. Therap. 3/2018)}, volume={1}, ISSN={2366-3987}, url={http://dx.doi.org/10.1002/ADTP.201870006}, DOI={10.1002/ADTP.201870006}, abstractNote={Acne Vulgaris The image representing article no. 1800035, by Jinqiang Wang, Qundong Shen, Zhen Gu and co-workers is a schematic illustration of an anti-acne microneedle swab for acne vulgaris treatment. The microneedle array can directly deliver therapeutics into inflammatory pilosebaceous unit in a reactive oxygen species (ROS)-responsive manner. Image courtesy of Yuqi Zhang.}, number={3}, journal={Advanced Therapeutics}, publisher={Wiley}, author={Zhang, Yuqi and Feng, Peijian and Yu, Jicheng and Yang, Jia and Zhao, Jiacheng and Wang, Jinqiang and Shen, Qundong and Gu, Zhen}, year={2018}, month={Jul}, pages={1870006} }
 @article{ruan_bu_hu_cheng_lu_gu_2018, title={Strategies of Combination Drug Delivery for Immune Checkpoint Blockades}, ISSN={2192-2640 2192-2659}, url={http://dx.doi.org/10.1002/ADHM.201801099}, DOI={10.1002/ADHM.201801099}, abstractNote={Abstract}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Ruan, Huitong and Bu, Linlin and Hu, Quanyin and Cheng, Hao and Lu, Weiyue and Gu, Zhen}, year={2018}, month={Dec}, pages={1801099} }
 @article{tang_su_huang_dinh_wang_vandergriff_hensley_cores_allen_li_et al._2018, title={Targeted repair of heart injury by stem cells fused with platelet nanovesicles}, volume={2}, ISSN={["2157-846X"]}, url={https://europepmc.org/articles/PMC5976251}, DOI={10.1038/s41551-017-0182-x}, abstractNote={Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types. The attachment of platelet nanovesicles to the surface of cardiac stem cells increases the retention of the cells delivered to the heart and reduces infarct size in rat and pig models of acute myocardial infarction.}, number={1}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Tang, Junnan and Su, Teng and Huang, Ke and Dinh, Phuong-Uyen and Wang, Zegen and Vandergriff, Adam and Hensley, Michael T. and Cores, Jhon and Allen, Tyler and Li, Taosheng and et al.}, year={2018}, month={Jan}, pages={17–26} }
 @article{xu_lu_luo_liu_cao_shen_li_liu_chen_chen_et al._2018, title={Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases}, volume={9}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/S41467-018-06522-5}, DOI={10.1038/S41467-018-06522-5}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Xu, Congfei and Lu, Zidong and Luo, Yingli and Liu, Yang and Cao, Zhiting and Shen, Song and Li, Hongjun and Liu, Jing and Chen, Kaige and Chen, Zhiyao and et al.}, year={2018}, month={Oct} }
 @article{zhang_yu_wen_chen_gu_2018, title={The potential of a microneedle patch for reducing obesity}, volume={15}, ISSN={["1744-7593"]}, DOI={10.1080/17425247.2018.1449831}, abstractNote={Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, USA; Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA}, number={5}, journal={EXPERT OPINION ON DRUG DELIVERY}, author={Zhang, Yuqi and Yu, Jicheng and Wen, Di and Chen, Guojun and Gu, Zhen}, year={2018}, pages={431–433} }
 @article{gu_chen_2018, title={Towards Enhancing Skin Drug Delivery}, volume={127}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2018.05.004}, abstractNote={Topical treatment of mild-to-moderate psoriasis with corticosteroids suffers from challenges that include reduced drug bioavailability at the desired site of action. The retention of therapeutics within the epidermis can safely treat skin inflammation, scaling, and erythema associated with psoriasis while avoiding possible side effects associated with systemic treatments. We successfully synthesized and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-fluocinolone acetonide (FLUO) conjugate that allows the controlled release of the FLUO to reduce skin inflammation. Additionally, the application of a hyaluronic acid (HA)-poly-L-glutamate cross polymer (HA-CP) vehicle boosted skin permeation. During in vitro and ex vivo analyses, we discovered that PGA-FLUO inhibited pro-inflammatory cytokine release, suggesting that polypeptidic conjugation fails to affect the anti-inflammatory activity of FLUO. Additionally, ex vivo human skin permeation studies using confocal microscopy revealed the presence of PGA-FLUO within the epidermis, but a minimal presence in the dermis, thereby reducing the likelihood of FLUO entering the systemic circulation. Finally, we demonstrated that PGA-FLUO applied within HA-CP effectively reduced psoriasis-associated phenotypes in an in vivo mouse model of human psoriasis while also lowering levels of pro-inflammatory cytokines in tissue and serum. Overall, our experimental results demonstrate that PGA-FLUO within an HA-CP penetration enhancer represents an effective topical treatment for psoriasis.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Gu, Zhen and Chen, Xiaoyuan}, year={2018}, month={Mar}, pages={1–2} }
 @article{ye_wang_zhang_hu_zhang_liu_wen_milligan_bellotti_huang_et al._2017, title={A melanin-mediated cancer immunotherapy patch}, volume={2}, ISSN={["2470-9468"]}, DOI={10.1126/sciimmunol.aan5692}, abstractNote={Transdermal microneedle patch integrated with whole tumor lysate containing melanin facilitates cancer immunotherapy upon near-infrared light irradiation.}, number={17}, journal={SCIENCE IMMUNOLOGY}, author={Ye, Yanqi and Wang, Chao and Zhang, Xudong and Hu, Quanyin and Zhang, Yuqi and Liu, Qi and Wen, Di and Milligan, Joshua and Bellotti, Adriano and Huang, Leaf and et al.}, year={2017}, month={Nov} }
 @article{qian_feng_yu_chen_hu_sun_xiao_hu_bellotti_shen_et al._2017, title={Anaerobe-Inspired Anticancer Nanovesicles}, volume={56}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201611783}, abstractNote={Abstract}, number={10}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Qian, Chenggen and Feng, Peijian and Yu, Jicheng and Chen, Yulei and Hu, Quanyin and Sun, Wujin and Xiao, Xuanzhong and Hu, Xiuli and Bellotti, Adriano and Shen, Qun-Dong and et al.}, year={2017}, month={Mar}, pages={2588–2593} }
 @misc{wang_sun_ye_bomba_gu_2017, title={Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs}, volume={7}, ISSN={["1838-7640"]}, DOI={10.7150/thno.19017}, abstractNote={The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.}, number={14}, journal={THERANOSTICS}, author={Wang, Chao and Sun, Wujin and Ye, Yanqi and Bomba, Hunter N. and Gu, Zhen}, year={2017}, pages={3504–3516} }
 @misc{lu_aimetti_langer_gu_2017, title={Bioresponsive materials}, volume={2}, ISSN={["2058-8437"]}, DOI={10.1038/natrevmats.2016.75}, number={1}, journal={NATURE REVIEWS MATERIALS}, author={Lu, Yue and Aimetti, Alex A. and Langer, Robert and Gu, Zhen}, year={2017}, month={Jan} }
 @misc{yu_zhang_kahkoska_gu_2017, title={Bioresponsive transcutaneous patches}, volume={48}, ISSN={["1879-0429"]}, DOI={10.1016/j.copbio.2017.03.001}, abstractNote={Transdermal drug delivery systems that utilize transcutaneous patches of arrayed microneedles have attracted increasing interest in medical practice as an alternative method to hypodermic injection. Over the past ten years, research has focused on leveraging physiological signals associated with diseases or skin-specific tissues to create bioresponsive patches that release drug directly in response to an internally-generated stimulus. This review surveys the recent advances in the development and use of bioresponsive transcutaneous patches for on-demand smart and precise drug delivery, exploiting different physiological signals including pH, serum glucose levels, and enzyme activity. The clinical potential of these devices, including challenges and opportunities, is also discussed.}, journal={CURRENT OPINION IN BIOTECHNOLOGY}, author={Yu, Jicheng and Zhang, Yuqi and Kahkoska, Anna R. and Gu, Zhen}, year={2017}, month={Dec}, pages={28–32} }
 @misc{cheng-gen_chen_feng_xiao_dong_yu_hu_shen_gu_2017, title={Conjugated polymer nanomaterials for theranostics}, volume={38}, ISSN={["1745-7254"]}, DOI={10.1038/aps.2017.42}, abstractNote={Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrared (NIR) imaging, two-photon (TP) imaging, photoacoustic (PA) imaging, and multimodal (MM) imaging, are introduced. Then, CPN-based photodynamic therapy (PDT) and photothermal therapy (PTT) are surveyed. A variety of stimuli-responsive CPN systems for drug delivery are also summarized, and the promising trends and translational challenges are discussed.}, number={6}, journal={ACTA PHARMACOLOGICA SINICA}, author={Cheng-gen, Qian and Chen, Yu-lei and Feng, Pei-jian and Xiao, Xuan-zhong and Dong, Mei and Yu, Ji-cheng and Hu, Quan-yin and Shen, Qun-dong and Gu, Zhen}, year={2017}, month={Jun}, pages={764–781} }
 @misc{hu_bomba_gu_2017, title={Engineering platelet-mimicking drug delivery vehicles}, volume={11}, ISSN={["2095-0187"]}, DOI={10.1007/s11705-017-1614-6}, number={4}, journal={FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING}, author={Hu, Quanyin and Bomba, Hunter N. and Gu, Zhen}, year={2017}, month={Dec}, pages={624–632} }
 @article{ma_xiao_yu_liu_cheng_song_zhang_li_wang_gu_et al._2017, title={Enhanced Cisplatin Chemotherapy by Iron Oxide Nanocarrier-Mediated Generation of Highly Toxic Reactive Oxygen Species}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b04269}, abstractNote={Reactive oxygen species (ROS) plays a key role in therapeutic effects as well as side effects of platinum drugs. Cisplatin mediates activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which triggers oxygen (O2) to superoxide radical (O2•-) and its downstream H2O2. Through the Fenton's reaction, H2O2 could be catalyzed by Fe2+/Fe3+ to the toxic hydroxyl radicals (•OH), which cause oxidative damages to lipids, proteins, and DNA. By taking the full advantage of Fenton's chemistry, we herein demonstrated tumor site-specific conversion of ROS generation induced by released cisplatin and Fe2+/Fe3+ from iron-oxide nanocarriers with cisplatin(IV) prodrugs for enhanced anticancer activity but minimized systemic toxicity.}, number={2}, journal={NANO LETTERS}, author={Ma, Ping'an and Xiao, Haihua and Yu, Chang and Liu, Jianhua and Cheng, Ziyong and Song, Haiqin and Zhang, Xinyang and Li, Chunxia and Wang, Jinqiang and Gu, Zhen and et al.}, year={2017}, month={Feb}, pages={928–937} }
 @article{lu_lin_chen_hu_liu_yu_gao_dickey_gu_2017, title={Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b04346}, abstractNote={Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.}, number={4}, journal={NANO LETTERS}, publisher={American Chemical Society (ACS)}, author={Lu, Yue and Lin, Yiliang and Chen, Zhaowei and Hu, Quanyin and Liu, Yang and Yu, Shuangjiang and Gao, Wei and Dickey, Michael D. and Gu, Zhen}, year={2017}, month={Apr}, pages={2138–2145} }
 @article{bakh_cortinas_weiss_langer_anderson_gu_dutta_strano_2017, title={Glucose-responsive insulin by molecular and physical design}, volume={9}, ISSN={["1755-4349"]}, DOI={10.1038/nchem.2857}, abstractNote={The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.}, number={10}, journal={NATURE CHEMISTRY}, author={Bakh, Naveed A. and Cortinas, Abel B. and Weiss, Michael A. and Langer, Robert S. and Anderson, Daniel G. and Gu, Zhen and Dutta, Sanjoy and Strano, Michael S.}, year={2017}, month={Oct}, pages={937–943} }
 @article{hu_yu_qian_lu_kahkoska_xie_jing_buse_gu_2017, title={H2O2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery}, volume={11}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.6b06892}, abstractNote={A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.}, number={1}, journal={ACS NANO}, author={Hu, Xiuli and Yu, Jicheng and Qian, Chenggen and Lu, Yue and Kahkoska, Anna R. and Xie, Zhigang and Jing, Xiabin and Buse, John B. and Gu, Zhen}, year={2017}, month={Jan}, pages={613–620} }
 @article{yu_qian_zhang_cui_zhu_shen_ligler_buse_gu_2017, title={Hypoxia and H2O2 Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b03848}, abstractNote={A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.}, number={2}, journal={NANO LETTERS}, author={Yu, Jicheng and Qian, Chenggen and Zhang, Yuqi and Cui, Zheng and Zhu, Yong and Shen, Qundong and Ligler, Frances S. and Buse, John B. and Gu, Zhen}, year={2017}, month={Feb}, pages={733–739} }
 @article{wang_sun_ye_hu_bomba_gu_2017, title={In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy}, volume={1}, ISSN={2157-846X}, url={http://dx.doi.org/10.1038/S41551-016-0011}, DOI={10.1038/S41551-016-0011}, number={2}, journal={Nature Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={Wang, Chao and Sun, Wujin and Ye, Yanqi and Hu, Quanyin and Bomba, Hunter N. and Gu, Zhen}, year={2017}, month={Jan} }
 @article{wang_sun_wright_wang_gu_2017, title={Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody}, volume={29}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201700761}, DOI={10.1002/ADMA.201700761}, abstractNote={Andrew Wang [Prof.], and Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA; Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC 27599, USA}, number={15}, journal={Advanced Materials}, publisher={Wiley}, author={Wang, Chao and Sun, Wujin and Wright, Grace and Wang, Andrew Z. and Gu, Zhen}, year={2017}, month={Apr} }
 @article{yu_zhang_he_sun_cao_cui_deng_gu_chen_2017, title={Injectable Thermosensitive Polypeptide-Based CDDP-Complexed Hydrogel for Improving Localized Antitumor Efficacy}, volume={18}, ISSN={1525-7797 1526-4602}, url={http://dx.doi.org/10.1021/ACS.BIOMAC.7B01374}, DOI={10.1021/ACS.BIOMAC.7B01374}, abstractNote={In this study, a type of novel thermosensitive polypeptide-based hydrogel with tunable gelation behavior through changing the content of carboxyl groups was developed for the purpose of improving the cisplatin (CDDP) release behavior and enhancing the localized antitumor efficiency. The introduction of carboxyl groups in methoxy-poly(ethylene glycol)-b-(poly(γ-ethyl-l-glutamate-co-l-glutamic acid) (mPEG-b-P(ELG-co-LG)) not only led to adjustable mechanical properties of the hydrogel but also significantly reduced the burst release of the drug through the complexation between the carboxyl groups of polypeptide and CDDP. Furthermore, both the good biocompatibility and the biodegradable properties of mPEG-b-P(ELG-co-LG) hydrogel were observed in vivo. Interestingly, the CDDP-complexed mPEG-b-P(ELG-co-LG) hydrogel exhibited significantly enhanced antitumor efficacy in vivo compared to the mPEG-b-PELG hydrogel loaded with CDDP without complexation, although a lower cytotoxicity and IC50 of the CDDP-complexed hydrogel was observed in vitro. Overall, the new type of injectable CDDP-complexed hydrogel may serve as an efficient platform for sustained CDDP delivery in localized tumor therapy.}, number={12}, journal={Biomacromolecules}, publisher={American Chemical Society (ACS)}, author={Yu, Shuangjiang and Zhang, Dianliang and He, Chaoliang and Sun, Wujin and Cao, Rangjuan and Cui, Shusen and Deng, Mingxiao and Gu, Zhen and Chen, Xuesi}, year={2017}, month={Nov}, pages={4341–4348} }
 @article{qian_feng_yu_chen_hu_sun_xiao_hu_bellotti_shen_et al._2017, title={Inside Cover: Anaerobe-Inspired Anticancer Nanovesicles (Angew. Chem. Int. Ed. 10/2017)}, volume={56}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/ANIE.201701131}, DOI={10.1002/ANIE.201701131}, abstractNote={An anaerobe-inspired drug delivery vehicle is described by Q. D. Shen, Z. Gu, and co-workers in their Communication on page 2588 ff. The biomimetic nanovesicles are stable in cells with normal physiological redox and oxygen balance. Upon disruption by external light stimuli, they show dual synergistic anticancer actions with enhanced therapeutic efficacy.}, number={10}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Qian, Chenggen and Feng, Peijian and Yu, Jicheng and Chen, Yulei and Hu, Quanyin and Sun, Wujin and Xiao, Xuanzhong and Hu, Xiuli and Bellotti, Adriano and Shen, Qun-Dong and et al.}, year={2017}, month={Feb}, pages={2516–2516} }
 @article{yu_zhang_sun_kahkoska_wang_buse_gu_2017, title={Insulin-Responsive Glucagon Delivery for Prevention of Hypoglycemia}, volume={13}, ISSN={1613-6810}, url={http://dx.doi.org/10.1002/SMLL.201603028}, DOI={10.1002/SMLL.201603028}, abstractNote={Hypoglycemia, the state of abnormally low blood glucose level, is an acute complication of insulin and sulfonylurea therapy in diabetes management. Frequent insulin dosing and boluses during daily diabetes care leads to an increased risk of dangerously low glucose levels, which can cause behavioral and cognitive disturbance, seizure, coma, and even death. This study reports an insulin‐responsive glucagon delivery method based on a microneedle (MN)‐array patch for the prevention of hypoglycemia. The controlled release of glucagon is achieved in response to elevated insulin concentration by taking advantage of the specific interaction between insulin aptamer and target insulin. Integrating a painless MN‐array patch, it is demonstrated that this insulin‐triggered glucagon delivery device is able to prevent hypoglycemia following a high‐dose insulin injection in a chemically induced type 1 diabetic mouse model.}, number={19}, journal={Small}, publisher={Wiley}, author={Yu, Jicheng and Zhang, Yuqi and Sun, Wujin and Kahkoska, Anna R. and Wang, Jinqiang and Buse, John B. and Gu, Zhen}, year={2017}, month={Mar}, pages={1603028} }
 @article{yu_zhang_sun_kahkoska_wang_buse_gu_2017, title={Insulin-responsive glucagon delivery for prevention of hypoglycemia}, volume={13}, DOI={10.1002/smll.201770108}, abstractNote={In article number 1603028, by Zhen Gu and co-workers, an insulin-responsive glucagon delivery device based on a microneedle (MN)-array patch is developed. Utilizing hyperinsulinemia as a dangerous signal, this “smart glucagon patch” can release glucagon to reduce the risk of hypoglycemia during diabetes management.}, number={19}, journal={Small (Weinheim An Der Bergstrasse, Germany)}, author={Yu, J. C. and Zhang, Y. Q. and Sun, W. J. and Kahkoska, A. R. and Wang, J. Q. and Buse, J. B. and Gu, Z.}, year={2017} }
 @article{zhang_liang_gu_chang_zhang_chen_ye_wang_tao_zeng_et al._2017, title={Investigation and intervention of autophagy to guide cancer treatment with nanogels}, volume={9}, ISSN={["2040-3372"]}, DOI={10.1039/c6nr07866d}, abstractNote={Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis. After inception by the cells, the nanogels were transported into multiple Rab positive vesicles including early endosomes (EEs), late endosomes (LEs), recycling endosomes (REs) and lipid droplets. Finally, these Rab positive vesicles were transported to lysosome. In addition, GLUT4 exocytosis vesicles could transport the nanogels out of the cells. Moreover, nanogels could induce autophagy and be sequestered in autophagosomes. The crosstalk between autophagosomes and Rab positive vesicles were investigated, we found that autophagosomes may receive nanogels through multiple Rab positive vesicles. Co-delivery of autophagy inhibitors such as chloroquine (CQ) and the chemotherapeutic drug doxorubicin (DOX) by nanogels blocked the autophagy induced by DOX greatly decreasing both of the volume and weight of the tumors in mice tumor models. Investigation and intervention of the autophagy pathway could provide a new method to improve the therapeutic effect of anticancer nanogels.}, number={1}, journal={NANOSCALE}, author={Zhang, Xudong and Liang, Xin and Gu, Jianjun and Chang, Danfeng and Zhang, Jinxie and Chen, Zhaowei and Ye, Yanqi and Wang, Chao and Tao, Wei and Zeng, Xiaowei and et al.}, year={2017}, month={Jan}, pages={150–163} }
 @article{lu_gu_2017, title={KIDNEY PHYSIOLOGYA size bandpass filter}, volume={12}, ISSN={["1748-3395"]}, DOI={10.1038/nnano.2017.200}, number={11}, journal={NATURE NANOTECHNOLOGY}, author={Lu, Yue and Gu, Zhen}, year={2017}, month={Nov}, pages={1023–1025} }
 @article{gu_nguyen_ganini_chen_jessen_gu_wang_shears_2017, title={KO of 5-InsP(7) kinase activity transforms the HCT116 colon cancer cell line into a hypermetabolic, growth-inhibited phenotype}, volume={114}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1702370114}, abstractNote={Significance}, number={45}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Gu, Chunfang and Nguyen, Hoai-Nghia and Ganini, Douglas and Chen, Zhaowei and Jessen, Henning J. and Gu, Zhen and Wang, Huanchen and Shears, Stephen B.}, year={2017}, month={Nov}, pages={11968–11973} }
 @misc{sun_hu_ji_wright_gu_2017, title={LEVERAGING PHYSIOLOGY FOR PRECISION DRUG DELIVERY}, volume={97}, ISSN={["1522-1210"]}, DOI={10.1152/physrev.00015.2016}, abstractNote={Physiological characteristics of diseases bring about both challenges and opportunities for targeted drug delivery. Various drug delivery platforms have been devised ranging from macro- to micro- and further into the nanoscopic scale in the past decades. Recently, the favorable physicochemical properties of nanomaterials, including long circulation, robust tissue and cell penetration attract broad interest, leading to extensive studies for therapeutic benefits. Accumulated knowledge about the physiological barriers that affect the in vivo fate of nanomedicine has led to more rational guidelines for tailoring the nanocarriers, such as size, shape, charge, and surface ligands. Meanwhile, progresses in material chemistry and molecular pharmaceutics generate a panel of physiological stimuli-responsive modules that are equipped into the formulations to prepare “smart” drug delivery systems. The capability of harnessing physiological traits of diseased tissues to control the accumulation of or drug release from nanomedicine has further improved the controlled drug release profiles with a precise manner. Successful clinical translation of a few nano-formulations has excited the collaborative efforts from the research community, pharmaceutical industry, and the public towards a promising future of smart drug delivery.}, number={1}, journal={PHYSIOLOGICAL REVIEWS}, author={Sun, Wujin and Hu, Quanyin and Ji, Wenyan and Wright, Grace and Gu, Zhen}, year={2017}, month={Jan}, pages={189–225} }
 @article{wang_zhang_archibong_ligler_gu_2017, title={Leveraging H2O2Levels for Biomedical Applications}, volume={1}, ISSN={2366-7478}, url={http://dx.doi.org/10.1002/ADBI.201700084}, DOI={10.1002/ADBI.201700084}, abstractNote={Hydrogen peroxide (H2O2)‐responsive materials have been employed as drug delivery or diagnostic systems to treat or detect diseases with abnormal oxidative stress. A number of H2O2‐responsive systems have been developed, and they have achieved great progress in controlled drug delivery for disease treatment. However, pathological sites with elevated H2O2 level, such as cancer and inflammation, have their own characteristics; therefore the material structures and the subsequent formulations should be reasonably designed to acquire maximized therapeutic effects. In this progress report, we overview the development of H2O2‐responsive functional groups for constructing H2O2‐responsive formulations, as well as the guidance for designing suitable formulations to treat each specific pathological condition. The challenges and perspectives in this field are also discussed.}, number={9}, journal={Advanced Biosystems}, publisher={Wiley}, author={Wang, Jinqiang and Zhang, Yuqi and Archibong, Edikan and Ligler, Frances S. and Gu, Zhen}, year={2017}, month={Jul}, pages={1700084} }
 @article{wang_ye_gu_2017, title={Local delivery of checkpoints antibodies}, volume={13}, ISSN={["2164-554X"]}, DOI={10.1080/21645515.2016.1223000}, abstractNote={ABSTRACT Immune checkpoint inhibitors (ICI) based cancer immunotherapy has recently attracted considerable interest in the field of cancer therapy. The relevant immunotherapeutic agents do not directly attack the tumor, but boost the body's immune system to recognize and kill cancer cells. In this commentary, recent efforts utilizing immunoengineering for local delivery of these immune checkpoint antibodies are introduced. Future opportunities and challenges in this research theme are also commented.}, number={1}, journal={HUMAN VACCINES & IMMUNOTHERAPEUTICS}, author={Wang, Chao and Ye, Yanqi and Gu, Zhen}, year={2017}, pages={245–248} }
 @article{zhang_liu_yu_yu_wang_qiang_gu_2017, title={Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment}, volume={11}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.7b04348}, abstractNote={Obesity is one of the most serious public health problems in the 21st century that may lead to many comorbidities such as type-2 diabetes, cardiovascular diseases, and cancer. Current treatments toward obesity including diet, physical exercise, pharmacological therapy, as well as surgeries are always associated with low effectiveness or undesired systematical side effects. In order to enhance treatment efficiency with minimized side effects, we developed a transcutaneous browning agent patch to locally induce adipose tissue transformation. This microneedle-based patch can effectively deliver browning agents to the subcutaneous adipocytes in a sustained manner and switch on the "browning" at the targeted region. It is demonstrated that this patch reduces treated fat pad size, increases whole body energy expenditure, and improves type-2 diabetes in vivo in a diet-induced obesity mouse model.}, number={9}, journal={ACS NANO}, author={Zhang, Yuqi and Liu, Qiongming and Yu, Jicheng and Yu, Shuangjiang and Wang, Jinqiang and Qiang, Li and Gu, Zhen}, year={2017}, month={Sep}, pages={9223–9230} }
 @misc{zhang_yu_kahkoska_gu_2017, title={Photoacoustic Drug Delivery}, volume={17}, ISSN={["1424-8220"]}, DOI={10.3390/s17061400}, abstractNote={Photoacoustic (PA) technology holds great potential in clinical translation as a new non-invasive bioimaging modality. In contrast to conventional optical imaging, PA imaging (PAI) enables higher resolution imaging with deeper imaging depth. Besides applications for diagnosis, PA has also been extended to theranostic applications. The guidance of PAI facilitates remotely controlled drug delivery. This review focuses on the recent development of PAI-mediated drug delivery systems. We provide an overview of the design of different PAI agents for drug delivery. The challenges and further opportunities regarding PA therapy are also discussed.}, number={6}, journal={SENSORS}, author={Zhang, Yuqi and Yu, Jicheng and Kahkoska, Anna R. and Gu, Zhen}, year={2017}, month={Jun} }
 @article{yan_yu_wang_gu_2017, title={Red Blood Cells for Drug Delivery}, volume={1}, ISSN={2366-9608}, url={http://dx.doi.org/10.1002/SMTD.201700270}, DOI={10.1002/SMTD.201700270}, abstractNote={Abstract}, number={12}, journal={Small Methods}, publisher={Wiley}, author={Yan, Junjie and Yu, Jicheng and Wang, Chao and Gu, Zhen}, year={2017}, month={Nov}, pages={1700270} }
 @article{wang_ye_sun_yu_wang_lawrence_buse_gu_2017, title={Red Blood Cells for Glucose-Responsive Insulin Delivery}, volume={29}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201606617}, abstractNote={Glucose‐responsive delivery of insulin mimicking the function of pancreatic β‐cells to achieve meticulous control of blood glucose (BG) would revolutionize diabetes care. Here the authors report the development of a new glucose‐responsive insulin delivery system based on the potential interaction between the glucose derivative‐modified insulin (Glc‐Insulin) and glucose transporters on erythrocytes (or red blood cells, RBCs) membrane. After being conjugated with the glucosamine, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of BG level in vivo. The delivery vehicle can be further simplified utilizing injectable polymeric nanocarriers coated with RBC membrane and loaded with Glc‐Insulin. The described work is the first demonstration of utilizing RBC membrane to achieve smart insulin delivery with fast responsiveness.}, number={18}, journal={ADVANCED MATERIALS}, author={Wang, Chao and Ye, Yanqi and Sun, Wujin and Yu, Jicheng and Wang, Jingqiang and Lawrence, David S. and Buse, John B. and Gu, Zhen}, year={2017}, month={May} }
 @article{hu_sun_qian_bomba_xin_gu_2017, title={Relay Drug Delivery for Amplifying Targeting Signal and Enhancing Anticancer Efficacy}, volume={29}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201605803}, abstractNote={A "relay drug delivery" system based on two distinct modules, which is composed of a signal transmission nanocarrier A (NCA ) that can specifically induce tumor blood vessel inflammation generation and an execution biomimetic nanocarrier B (NCB ) that can accumulate at the tumor site by receiving the broadcasting signals generated by NCA , is developed for amplifying active tumor targeting signal and enhancing antitumor therapy.}, number={13}, journal={ADVANCED MATERIALS}, author={Hu, Quanyin and Sun, Wujin and Qian, Chenggen and Bomba, Hunter N. and Xin, Hongliang and Gu, Zhen}, year={2017}, month={Apr} }
 @article{zhang_wang_yu_gu_2017, title={Smart materials and systems as artificial pancreas for diabetes treatment}, volume={25}, journal={Smart materials for tissue engineering: applications}, author={Zhang, Y. Q. and Wang, M. Z. and Yu, J. C. and Gu, Z.}, year={2017}, pages={358–381} }
 @article{hu_zhang_xie_jing_bellotti_gu_2017, title={Stimuli-Responsive Polymersomes for Biomedical Applications}, volume={18}, ISSN={["1526-4602"]}, DOI={10.1021/acs.biomac.6b01704}, abstractNote={Polymersomes, the structural analogues of liposomes, are hollow structures enclosed by a bilayer membrane made from amphiphilic copolymers. Polymersomes have been proposed to mimic the structure and properties of cellular membranes and viral capsids. Excellent robustness and stability, chemical versatility for tunable membrane properties and surface functionalization make polymersomes attractive candidates for drug delivery, diagnostic imaging, nanoreactor vessels, and artificial organelles. In further biomimetic strategies, stimuli-responsive polymersomes that can recognize various external physical or internal biological environmental stimuli and conduct "on demand" release in dose-, spatial-, and temporal-controlled fashions have been widely developed. This Perspective focuses on recent advances in stimuli-responsive polymersomes and their potential biomedical applications. Representative examples of each stimulus, the advantages and limitations of different strategies, and the future opportunities and challenges are discussed.}, number={3}, journal={BIOMACROMOLECULES}, author={Hu, Xiuli and Zhang, Yugi and Xie, Zhigang and Jing, Xiabin and Bellotti, Adriano and Gu, Zhen}, year={2017}, month={Mar}, pages={649–673} }
 @article{chen_wang_sun_archibong_kahkoska_zhang_lu_ligler_buse_gu_2017, title={Synthetic beta cells for fusion-mediated dynamic insulin secretion}, volume={14}, ISSN={1552-4450 1552-4469}, url={http://dx.doi.org/10.1038/NCHEMBIO.2511}, DOI={10.1038/nchembio.2511}, abstractNote={Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AβCs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AβCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin 'exocytosis'.}, number={1}, journal={Nature Chemical Biology}, publisher={Springer Science and Business Media LLC}, author={Chen, Zhaowei and Wang, Jinqiang and Sun, Wujin and Archibong, Edikan and Kahkoska, Anna R and Zhang, Xudong and Lu, Yue and Ligler, Frances S and Buse, John B and Gu, Zhen}, year={2017}, month={Oct}, pages={86–93} }
 @article{wang_ye_hu_bellotti_gu_2017, title={Tailoring Biomaterials for Cancer Immunotherapy: Emerging Trends and Future Outlook}, volume={29}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201606036}, abstractNote={Cancer immunotherapy, as a paradigm shift in cancer treatment, has recently received tremendous attention. The active cancer vaccination, immune checkpoint blockage (ICB) and chimeric antigen receptor (CAR) for T‐cell‐based adoptive cell transfer are among these developments that have achieved a significant increase in patient survival in clinical trials. Despite these advancements, emerging research at the interdisciplinary interface of cancer biology, immunology, bioengineering, and materials science is important to further enhance the therapeutic benefits and reduce side effects. Here, an overview of the latest studies on engineering biomaterials for the enhancement of anticancer immunity is given, including the perspectives of delivery of immunomodulatory therapeutics, engineering immune cells, and constructing immune‐modulating scaffolds. The opportunities and challenges in this field are also discussed.}, number={29}, journal={ADVANCED MATERIALS}, author={Wang, Chao and Ye, Yanqi and Hu, Quanyin and Bellotti, Adriano and Gu, Zhen}, year={2017}, month={Aug} }
 @misc{sun_gu_2017, title={Tailoring non-viral delivery vehicles for transporting genome-editing tools}, volume={60}, DOI={10.1007/s40843-016-5154-4}, abstractNote={The CRISPR-Cas system, especially the type II CRISPR-Cas9 system from Streptococcuspyogenes, has rapidly emerged as a popular genome editing tool. The development of Cas9 derivatives further expanded the toolbox of CRISPRCas9 based genome editing kit. However, therapeutic translation of the CRISPR-Cas9 system in vivo is severely impeded by the absence of an appropriate delivery carrier. The complexity and high molecular weight of the CRISPR-Cas9 system, together with the physiological barriers for nucleus targeted cargo transportation have made it a huge challenge for in vivo therapeutic CRISPR-Cas9 delivery. Currently, the main stream carriers for systemic delivery of CRISPR-Cas9 are viral based, such as adeno-associated virus. However, the safety concerns surrounding viral vectors call for the development of non-viral nanocarriers. In this review, we survey the recent advances in the development of non-viral delivery systems for CRISPR-Cas9. Challenges and future directions in this field are also discussed.}, number={6}, journal={Science China-Materials}, author={Sun, W. J. and Gu, Z.}, year={2017}, pages={511–515} }
 @article{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2017, title={Thrombin-responsive transcutaneous patch for auto-anticoagulant regulation}, volume={29}, DOI={10.1002/adma.201770028}, abstractNote={A thrombin-responsive microneedle-based transcutaneous patch is developed by C. M. Gallippi, Y. Zhu, Z. Gu, and co-workers, as demonstrated in article 1604043. The anticoagulant drug heparin is loaded into the hyaluronic acid needles through a thrombin cleavable peptide linker. This heparin patch can sense the thrombin level in blood vessels and autoregulate blood coagulation in a long-term manner. Cover design credit: Yuqi Zhang.}, number={4}, journal={Advanced Materials}, author={Zhang, Y. Q. and Yu, J. C. and Wang, J. Q. and Hanne, N. J. and Cui, Z. and Qian, C. G. and Wang, C. and Xin, H. L. and Cole, Jacqueline and Gallippi, C. M. and et al.}, year={2017} }
 @article{di_yu_wang_yao_suo_ye_pless_zhu_jing_gu_2017, title={Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules}, volume={10}, ISSN={1998-0124 1998-0000}, url={http://dx.doi.org/10.1007/S12274-017-1500-Z}, DOI={10.1007/s12274-017-1500-z}, number={4}, journal={Nano Research}, publisher={Springer Nature}, author={Di, Jin and Yu, Jicheng and Wang, Qun and Yao, Shanshan and Suo, Dingjie and Ye, Yanqi and Pless, Matthew and Zhu, Yong and Jing, Yun and Gu, Zhen}, year={2017}, month={Mar}, pages={1393–1402} }
 @article{sun_gu_2016, title={ATP-Responsive Drug Delivery Systems}, volume={13}, ISSN={["1744-7593"]}, DOI={10.1517/17425247.2016.1140147}, abstractNote={Advances in material science brought about a wide range of drug delivery systems, from traditional bulk controlled release formulations to modern nanotechnology based carriers, for improved drug efficacy. A wide collection of nanoparticle frameworks, like metallic nanoparticles, liposomes, polymeric nanogels, protein or DNA nanoassemblies, were employed in constructing nanocarriers. Basic nanoparticle framework can be viewed as the chassis of a motor vehicle, upon which various functional modules could be installed, such as targeting ligands for vehicle “steering”, drug binding and environment-sensing moieties for cargo loading and unloading. Uncontrolled drug release from nanocarriers along their way to diseased areas significantly compromises the therapeutic effects while increasing the risk of side effects. The concept of “on-demand” therapeutics would be more promising when the nanocarriers are “smart” to perceive their surrounding environment and react correspondingly. To generate these “smart” formulations for precise delivery, numerous types of stimuli-responsive materials were developed and incorporated into the nanocarriers [1]. 
 
Our group has been devoted to the development of “smart” nanocarriers responsive to a variety of triggers for cancer and diabetes treatment. For example, external physical triggers, like focused ultrasound [2] or tensile strains [3] were applied as hints to control drug dosing. Internal physiological triggers, like overexpressed enzymes (such as furin [4] or hyaluronidase [5]), acidic environment [6], reducing gradients [7], hypoxia [8] or elevated blood glucose levels [9] were also harnessed for controlling drug release. 
 
In this editorial, we discuss an emerging strategy utilizing the “molecular unit of currency” in biological energy transfer - ATP - as a trigger for therapeutic delivery. The sharp concentration contrast between extracellular (<0.4 mM) and intracellular (1-10 mM) environments makes ATP a feasible cue for regulating drug release [5].}, number={3}, journal={EXPERT OPINION ON DRUG DELIVERY}, author={Sun, Wujin and Gu, Zhen}, year={2016}, month={Mar}, pages={311–314} }
 @article{qian_chen_zhu_yu_zhang_feng_tang_hu_sun_lu_et al._2016, title={ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging}, volume={6}, ISSN={["1838-7640"]}, DOI={10.7150/thno.14843}, abstractNote={Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging.}, number={7}, journal={THERANOSTICS}, author={Qian, Chenggen and Chen, Yulei and Zhu, Sha and Yu, Jicheng and Zhang, Lei and Feng, Peijian and Tang, Xin and Hu, Quanyin and Sun, Wujin and Lu, Yue and et al.}, year={2016}, pages={1053–1064} }
 @article{qian_yu_chen_hu_xiao_sun_wang_feng_shen_gu_2016, title={Anticancer Therapy: Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy (Adv. Mater. 17/2016)}, volume={28}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201670115}, DOI={10.1002/ADMA.201670115}, abstractNote={A light-activated hypoxia-responsive drug-delivery vehicle is described by Q.-D. Shen, Z. Gu, and co-workers on page 3313. This conjugated-polymer-based nanocarrier can be activated by photoirradiation, producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargo inside tumor cells for enhanced anticancer efficacy.}, number={17}, journal={Advanced Materials}, publisher={Wiley}, author={Qian, Chenggen and Yu, Jicheng and Chen, Yulei and Hu, Quanyin and Xiao, Xuanzhong and Sun, Wujin and Wang, Chao and Feng, Peijian and Shen, Qun-Dong and Gu, Zhen}, year={2016}, month={Apr}, pages={3226–3226} }
 @inproceedings{hu_gu_2016, title={Cell membrane-mediated anticancer drug delivery}, volume={1224}, booktitle={Nanotechnology: delivering on the promise, vol 2}, author={Hu, Q. Y. and Gu, Z.}, year={2016}, pages={197–211} }
 @article{ye_yu_wang_nguyen_walker_buse_gu_2016, title={Drug Delivery: Microneedles Integrated with Pancreatic Cells and Synthetic Glucose-Signal Amplifiers for Smart Insulin Delivery (Adv. Mater. 16/2016)}, volume={28}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201670112}, DOI={10.1002/ADMA.201670112}, abstractNote={A bio-responsive microneedle-based patch, integrated with a rhodamine-stained glucose-signal amplifier and calcein-AM-stained pancreatic β-cell capsules, is developed by Z. Gu and co-workers. This "smart cell patch", described on page 3115, effectively regulates the blood glucose level of type-1 diabetic mice, achieving a reduction for over 10 h. Image credit: Yanqi Ye.}, number={16}, journal={Advanced Materials}, publisher={Wiley}, author={Ye, Yanqi and Yu, Jicheng and Wang, Chao and Nguyen, Nhu-Y and Walker, Glenn M. and Buse, John B. and Gu, Zhen}, year={2016}, month={Apr}, pages={3223–3223} }
 @article{zhao_jiang_lv_wang_lv_wang_liu_liu_hu_sun_et al._2016, title={Dual targeted nanocarrier for brain ischemic stroke treatment}, volume={233}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2016.04.038}, abstractNote={Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Zhao, Yue and Jiang, Yan and Lv, Wei and Wang, Zhongyuan and Lv, Lingyan and Wang, Baoyan and Liu, Xin and Liu, Yang and Hu, Quanyin and Sun, Wujin and et al.}, year={2016}, month={Jul}, pages={64–71} }
 @article{zhang_yu_zhu_gu_2016, title={Elastic drug delivery: could treatments be triggered by patient movement?}, volume={11}, ISSN={["1748-6963"]}, DOI={10.2217/nnm.15.197}, abstractNote={NanomedicineVol. 11, No. 4 EditorialFree AccessElastic drug delivery: could treatments be triggered by patient movement?Yuqi Zhang, Jicheng Yu, Yong Zhu & Zhen GuYuqi Zhang Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author, Jicheng Yu Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author, Yong Zhu Department of Mechanical & Aerospace Engineering, North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this author & Zhen Gu*Author for correspondence: E-mail Address: zgu@email.unc.edu Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill & North Carolina State University, Raleigh, NC 27695, USASearch for more papers by this authorPublished Online:19 Jan 2016https://doi.org/10.2217/nnm.15.197AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: drug deliverymechanical-responsivenanoparticlewearable devicesFirst draft submitted: 22 October 2015; Accepted for publication: 12 November 2015; Published online: 19 January 2016Nanoparticle-based drug delivery systems have drawn extensive attention for treating a broad range of diseases during the last few decades [1,2]. In order to enhance therapeutic efficacy, reduce side effects and prolong action time, vast efforts have been dedicated to the development of on-demand, precise drug release. In light of this, numerous stimuli-responsive designs have been exploited, including external triggers like mechanical force, temperature, light, ultrasound, electric current and magnetic field as well as internal factors like pH, redox, enzymes, ATP and hypoxia [3–8]. Compared with other stimuli-responsive designs, the macroscopic mechanical force-mediated approach, as one of the most promising strategies, possesses several advantages. It can be generated on-demand during the patients’ daily movement, such as tension in bone joints, tendons and muscles, or compression in cartilage and bones. Therefore, a self-administrated therapy can be readily achieved without requirement of additional instrumentations. In addition, in contrast to the inaccurate internal factors due to the complicated physiological environment, the degree of stretch or compression is more conveniently controlled by the patient themselves, leading to a precise dosage-, spatial- and temporal-controllable administration of drug release.Physical deformation of drug carriers supported on an elastomer substrate caused by stretch or compression is one of the most important strategies for mechanical force-triggered release. Mooney group designed a compression-responsive system for controlled release of growth factor [9]. Inspired by the natural extracellular matrices, they developed a hydrogel with reversible binding of drug as synthetic extracelluar matrices. The physical-loaded hydrogel could respond to repeated compression stimulus and as a result released free drug. Afterward, the matrices could be refilled by free drug during relaxation via dissociation of previously bound drug. Using VEGF as a model drug in in vivo studies, they demonstrated that the implanted hydrogels allowed an increase in VEGF concentration near implantation site as applying mechanical signals, subsequently leading to a local enhanced vascularization. In another case, Jeong group developed a strain-sensitive patch consisting of arrays of microcapsules onto a rubbery substrate for drug release [10]. When stretch was applied to the elastomer substrate, the volume of the stretchable microcapsules encapsulating cargoes decreased accordingly with the substrate, then pumping out the preloaded molecules. Under different degrees of mechanical stretching, the release rate and amount of cargoes could be adjusted. This patch has the potential to respond to body motions, even to the mechanical stretching of organs, muscles and tendons when it is implanted into body.We have recently developed a multipurpose wearable, tensile strain-triggered drug delivery device, which comprised of a stretchable elastomer and microgel depots containing drug-loaded nanoparticles [11]. The drugs can be continuously released from the nanoparticles and temporarily stored in the microgels. When applying a tensile strain, the drugs were released from micro-depots due to the enlarged surface area for diffusion and Poisson's ratio-induced compression toward the microgels. Therefore, a sustained drug release can be conveniently achieved by daily body motion, while a pulsatile release is able to be controlled through intentional administration. We demonstrated that this device could be simply attached to a finger joint, and stretched to trigger the drug release when the finger is flexed for multiple cycles, which allowed patients to control the dose and release timing of antibacterial drug on their own.Furthermore, we integrated this stretch-sensitive device with a microneedle array patch for on-demand transcutaneous insulin delivery [3], which allowed the blood glucose level of mice to decline quickly to a normoglycemic range within 0.5 h. Meanwhile, the obvious pulsatile and continuous reduction in blood glucose level were observed when applying a strain with an interval of 4 h. Based on this technology, the diabetic patients can easily maintain normoglycemia through simple joint movement instead of a traditional painful insulin injection. This skin-mountable device can be further extended for anti-inflammatory, anti-infective drug or painkiller delivery. More importantly, this facile strategy allows immediate medical treatment in emergency situation by patient's simple body movement.Besides the direct drug release via changing diffusion area or pumping out caused by physical deformation, tension or compression can also generate energy to change the physical properties of drug carriers. For example, Pioletti group exploited dissipation properties of hydrogel as an internal heat source to trigger the thermal-sensitive drug release instead of additional external heat source [12]. Self heating was quickly produced after 5 min cyclic mechanical loading. The increased temperature further caused the shrinkage of thermal-responsive nanoparticles entrapped in the hydrogel and subsequent drug release.In addition, mechanical stretch or compression is able to tune the molecular conformation and intermolecular interaction between host molecule and guest molecule, resulting in a force-triggered drug release [13,14]. Based on this phenomenon, Ariga group reported a mechanically controlled monolayer formed by a steroid cyclophane molecule with a cyclic core linked to four steroid moieties via the flexible L-lysine spacer [13]. The applied compression could lead to a cavity-forming conformation of the cyclophane. Therefore, the hydrophobic model drug was easily trapped in this hydrophobic cavity. In contrast, expansion of the monolayer could release the encapsulated drug through the molecular transformation from cavity to planarity. Similarly, they developed a mechanical stimulus-activated β-cyclodextrin (CyD)-crosslinked alginate gel [15]. As applying mild mechanical compression, the model drug ondansetron, the entrapped guest, could be released from the host CyD moieties, due to the change in inclusion ability of CyD. The host–guest interactions dominated by van der Waals interactions and hydrogen bonds in a gel matrix can be more easily broken than covalent bonds, which provide a convenient on-demand administration of medicines operated intentionally by the patient.The research and development of patients’ movement-controlled drug delivery systems hold promise in improving patients’ compliance by providing a self-directed and on-demand treatment. Nonetheless, there are still many remaining challenges for clinical development. For example, the current systems cannot precisely control the release dose of therapeutics. A fundamental study on the dynamic relationships between the phase transitions of materials and the relevant release profile should be closely investigated. Moreover, regarding the different movement extent and ability for different individuals, how to generate a personalized platform and consistently apply the mechanical trigger signal are difficult tasks ahead that need to be addressed. Integration of this device with other wearable modalities to monitor the real-time physiological signals (e.g., electrocardiograph, blood glucose levels or body temperature [16,17]) and motion signals [18,19] might be able to provide feedback to guide the precise, personalized drug delivery. Last but not least, good biocompatibility and biodegradability for materials is extremely important for further translation of the elastic drug delivery system. Tailoring materials mimicking the structures and composites of natural systems offer a promising strategy [5,20].Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Jiang T, Mo R, Bellotti A, Zhou J, Gu Z. Gel–liposome‐mediated co‐delivery of anticancer membrane‐associated proteins and small‐molecule drugs for enhanced therapeutic efficacy. Adv. Funct. Mater. 24(16), 2295–2304 (2014).Crossref, CAS, Google Scholar2 Sun W, Jiang T, Lu Y, Reiff M, Mo R, Gu Z. Cocoon-like self-degradable dna nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 136(42), 14722–14725 (2014).Crossref, Medline, CAS, Google Scholar3 Yu J, Zhang Y, Ye Y et al. Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery. Proc. Natl Acad. Sci. USA 112(27), 8260–8265 (2015).Crossref, Medline, CAS, Google Scholar4 Mo R, Jiang T, Disanto R, Tai W, Gu Z. ATP-triggered anticancer drug delivery. Nat. Commun. 5, 3364 (2014).Crossref, Medline, Google Scholar5 Lu Y, Sun W, Gu Z. Stimuli-responsive nanomaterials for therapeutic protein delivery. J. Control. Release 194, 1–19 (2014).Crossref, Medline, CAS, Google Scholar6 Wu Z, Wu Y, He W, Lin X, Sun J, He Q. Self‐propelled polymer‐based multilayer nanorockets for transportation and drug release. Angew. Chem. Int. Ed. Engl. 52(27), 7000–7003 (2013).Crossref, Medline, CAS, Google Scholar7 Choi SW, Zhang Y, Xia Y. A temperature‐sensitive drug release system based on phase‐change materials. Angew. Chem. Int. Ed. Engl. 49(43), 7904–7908 (2010).Crossref, Medline, CAS, Google Scholar8 Zhang Y, Yin Q, Yin L, Ma L, Tang L, Cheng J. Chain‐shattering polymeric therapeutics with on‐demand drug‐release capability. Angew. Chem. Int. Ed. Engl. 52(25), 6435–6439 (2013).Crossref, Medline, CAS, Google Scholar9 Lee KY, Peters MC, Anderson KW, Mooney DJ. Controlled growth factor release from synthetic extracellular matrices. Nature 408(6815), 998–1000 (2000).Crossref, Medline, CAS, Google Scholar10 Hyun DC, Moon GD, Park CJ, Kim BS, Xia Y, Jeong U. Strain‐controlled release of molecules from arrayed microcapsules supported on an elastomer substrate. Angew. Chem. Int. Ed. Engl. 50(3), 724–727 (2011).Crossref, Medline, CAS, Google Scholar11 Di J, Yao S, Ye Y et al. Stretch-triggered drug delivery from wearable elastomer films containing therapeutic depots. ACS Nano 9(9), 9407–9415 (2015).Crossref, Medline, CAS, Google Scholar12 Moghadam MN, Kolesov V, Vogel A, Klok H-A, Pioletti DP. Controlled release from a mechanically-stimulated thermosensitive self-heating composite hydrogel. Biomaterials 35(1), 450–455 (2014).Crossref, Medline, CAS, Google Scholar13 Ariga K, Terasaka Y, Sakai D, Tsuji H, Kikuchi J-I. Piezoluminescence based on molecular recognition by dynamic cavity array of steroid cyclophanes at the air-water interface. J. Am. Chem. Soc. 122(32), 7835–7836 (2000).Crossref, CAS, Google Scholar14 Michinobu T, Shinoda S, Nakanishi T et al. Mechanical control of enantioselectivity of amino acid recognition by cholesterol-armed cyclen monolayer at the air-water interface. J. Am. Chem. Soc. 128(45), 14478–14479 (2006).Crossref, Medline, CAS, Google Scholar15 Izawa H, Kawakami K, Sumita M, Tateyama Y, Hill JP, Ariga K. β-Cyclodextrin-crosslinked alginate gel for patient-controlled drug delivery systems: regulation of host–guest interactions with mechanical stimuli. J. Mater. Chem. B 1(16), 2155–2161 (2013).Crossref, CAS, Google Scholar16 Myers AC, Huang H, Zhu Y. Wearable silver nanowire dry electrodes for electrophysiological sensing. RSC Adv. 5(15), 11627–11632 (2015).Crossref, CAS, Google Scholar17 Kim D-H, Lu N, Ma R et al. Epidermal electronics. Science 333(6044), 838–843 (2011).Crossref, Medline, CAS, Google Scholar18 Yao S, Zhu Y. Wearable multifunctional sensors using printed stretchable conductors made of silver nanowires. Nanoscale 6(4), 2345–2352 (2014).Crossref, Medline, CAS, Google Scholar19 Yao S, Zhu Y. Nanomaterial‐enabled stretchable conductors: strategies, materials and devices. Adv. Mater. 27(9), 1480–1511 (2015).Crossref, Medline, CAS, Google Scholar20 Mitragotri S, Anderson DG, Chen X et al. Accelerating the translation of nanomaterials in biomedicine. ACS Nano 9(7), 6644–6654 (2015).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByExternal stimuli-responsive drug delivery systemsMechanical on-off gates for regulation of drug release in cutaneous or musculoskeletal tissue repairsMaterials Science and Engineering: C, Vol. 115Biomechano-Interactive Materials and Interfaces7 June 2018 | Advanced Materials, Vol. 30, No. 31Nanomaterial‐Enabled Wearable Sensors for Healthcare30 November 2017 | Advanced Healthcare Materials, Vol. 7, No. 1 Vol. 11, No. 4 Follow us on social media for the latest updates Metrics History Published online 19 January 2016 Published in print February 2016 Information© Future Medicine LtdKeywordsdrug deliverymechanical-responsivenanoparticlewearable devicesFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download}, number={4}, journal={NANOMEDICINE}, author={Zhang, Yuqi and Yu, Jicheng and Zhu, Yong and Gu, Zhen}, year={2016}, pages={323–325} }
 @article{hu_qian_sun_wang_chen_bomba_xin_shen_gu_2016, title={Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus}, volume={28}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201603463}, abstractNote={A platelet-membrane-coated biomimetic nanocarrier, which can sequentially target the bone microenvironment and myeloma cells to enhance the drug availability at the myeloma site and decrease off-target effects, is developed for inhibiting multiple myeloma growth and simultaneously eradicating thrombus complication.}, number={43}, journal={ADVANCED MATERIALS}, author={Hu, Quanyin and Qian, Chenggen and Sun, Wujin and Wang, Jinqiang and Chen, Zhaowei and Bomba, Hunter N. and Xin, Hongliang and Shen, Qundong and Gu, Zhen}, year={2016}, month={Nov}, pages={9573-+} }
 @article{lv_jiang_liu_wang_lv_zhao_shi_hu_xin_xu_et al._2016, title={Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles}, volume={13}, ISSN={["1543-8384"]}, DOI={10.1021/acs.molpharmaceut.6b00523}, abstractNote={Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG-PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of in vitro antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC50 were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50 were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. In vivo distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The in vivo antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity.}, number={10}, journal={MOLECULAR PHARMACEUTICS}, author={Lv, Lingyan and Jiang, Yan and Liu, Xin and Wang, Baoyan and Lv, Wei and Zhao, Yue and Shi, Huihui and Hu, Quanyin and Xin, Hongliang and Xu, Qunwei and et al.}, year={2016}, month={Oct}, pages={3506–3517} }
 @article{wang_ye_hochu_sadeghifar_gu_2016, title={Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody}, volume={16}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.5b05030}, abstractNote={Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self-dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti-CTLA-4) to achieve combination therapy for enhancing antitumor efficacy.}, number={4}, journal={NANO LETTERS}, author={Wang, Chao and Ye, Yanqi and Hochu, Gabrielle M. and Sadeghifar, Hasan and Gu, Zhen}, year={2016}, month={Apr}, pages={2334–2340} }
 @article{yu_zhang_hu_wright_gu_2016, title={Hypoxia-Sensitive Materials for Biomedical Applications}, volume={44}, ISSN={["1573-9686"]}, DOI={10.1007/s10439-016-1578-6}, abstractNote={Hypoxia is a typical hallmark of various diseases, including cancer, ischemic diseases, and stroke. It is also associated with the disease progression. Therefore, it is critical to develop an effective strategy to target the hypoxic region for diagnosis and treatment. In this review, we summarize recent progress in the development of hypoxia-responsive systems for imaging, sensing and therapy. Two types of hypoxia-sensitive systems, the hypoxia inducible factor-1 based systems and bioreductive molecule based systems, were reviewed with comments on their advantages and limitations. Future opportunities and challenges are also discussed in the end.}, number={6}, journal={ANNALS OF BIOMEDICAL ENGINEERING}, author={Yu, Jicheng and Zhang, Yuqi and Hu, Xiuli and Wright, Grace and Gu, Zhen}, year={2016}, month={Jun}, pages={1931–1945} }
 @article{wang_sun_wright_wang_gu_2016, title={Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and Anti-PD1 Antibody}, volume={28}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201506312}, abstractNote={Inflammation-triggered combination delivery of anti-PD-1 antibody and CpG oligodeoxynucleotides (CpG ODNs) has been demonstrated to prevent cancer relapse utilizing postsurgical inflammatory response. The controlled release of anti-PD1 and CpG ODN by CpG DNA-based "nano-cocoons" can induce considerable immune response, which in turn significantly prolongs the survival time of mice.}, number={40}, journal={ADVANCED MATERIALS}, author={Wang, Chao and Sun, Wujin and Wright, Grace and Wang, Andrew Z. and Gu, Zhen}, year={2016}, month={Oct}, pages={8912–8920} }
 @article{yu_zhang_sun_wang_ranson_ye_weng_gu_2016, title={Internalized compartments encapsulated nanogels for targeted drug delivery}, volume={8}, ISSN={["2040-3372"]}, DOI={10.1039/c5nr08895j}, abstractNote={Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system.}, number={17}, journal={NANOSCALE}, author={Yu, Jicheng and Zhang, Yuqi and Sun, Wujin and Wang, Chao and Ranson, Davis and Ye, Yanqi and Weng, Yuyan and Gu, Zhen}, year={2016}, pages={9178–9184} }
 @article{gu_2016, title={Introduction to special issue on “Responsive Materials and Systems: Toward Smart and Precision Medications”}, volume={1}, ISSN={2380-6761}, url={http://dx.doi.org/10.1002/BTM2.10045}, DOI={10.1002/BTM2.10045}, abstractNote={Spurred by advances in materials chemistry, molecular pharmaceutics and micro/nanobiotechnology, stimuli-responsive “smart” materials and systems have been studied extensively for various applications, including drug delivery, diagnosis, tissue engineering, and biomedical devices. In drug delivery, the dosage-, spatialand/or temporalcontrolled release of therapeutics significantly enhances the treatment efficacy in a precise manner. The development of stimuli-responsive materials also allows noninvasive or minimally invasive monitoring in real-time for achieving next-generation diagnostics. In addition, the smart systems with the capability of communicating and interacting with cells are highly desirable for engineering regenerative medications and biomedical devices. This theme issue focuses on the responsive materials and systems for a range of biomedical applications, with a collection of ten relevant research or review papers. For diabetes treatment, Mitragotri and coworkers describe a novel mucoadhesive intestinal device entrapped in a capsule with a pH-responsive enteric coating for oral delivery of insulin. This device loadedwith insulin can effectively decrease blood glucose levels of diabetic rats. Gu and coworkers summarize a variety of stimuli-responsive delivery systems for diabetes treatment, including the pH-sensitive materials for oral delivery, the glucose-responsive delivery systems, and the on-demand delivery approaches by external ultrasound or light. For cancer therapy, Tong and Feng discuss general principles in polymer-drug conjugate design such as the synthetic strategies, the choice of the responsive linkers between the drug and polymer, and the in vivo delivery barriers. Liu and Liang review reactive oxygen species (ROS)-responsive system aswell as multiple stimuli systems for enhanced delivery of therapeutics. For tissue engineering, Hammond and collaborators develop nanoscale polyelectrolyte complexes to deliver insulinlike growth factor-1 (IGF-1) for cartilage repair. They demonstrate IGF-1 is released by nanocomplexes within the joint space over four weeks, protecting cartilage from degradation andmitigating joint inflammation. Remote utilization of physical triggers, such as light, magnetic force and temperature to achieve spatiotemporal activation is an emerging research topic in this field. Lovell and Miranda discuss different mechanisms of the light-induced liposome permeabilization for controlled drug delivery, including light-induced oxidation, photocrosslinking, photoisomerization, photocleavage, and photothermal release. Xu and coworkers describe the development of near-infrared light-responsive liposomes for enhanced gene transfection through the photothermal effect. Gaharwar and coworkers review the applications of smart hydrogels based on magnetic nanoparticles and thermoresponsive polymers in therapeutic drug delivery, bioimaging, and regenerative medicine. In the remainder of this issue, Webber focuses on the preparation of responsive self-assembled materials for biomedical applications, including engineering therapeutics and devices for biological sensing and disease diagnostics; Cui and coworkers review peptide-based supramolecular nanostructures and hydrogels for biological stimulitriggered delivery of biologics. Collectively, this issue highlights the exciting research work and key advances in leveraging responsive materials for smart and precision medications, the clinical translation of which would revolutionize health care, profoundly enhancing patients’ health and improving their quality of life.}, number={3}, journal={Bioengineering & Translational Medicine}, publisher={Wiley}, author={Gu, Zhen}, year={2016}, month={Sep}, pages={235–236} }
 @article{qian_yu_chen_hu_xiao_sun_wang_feng_shen_gu_2016, title={Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy}, volume={28}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201505869}, abstractNote={A light-activated hypoxia-responsive conjugated polymer-based nanocarrier is developed for efficiently producing singlet oxygen ((1) O2 ) and inducing hypoxia to promote release of its cargoes in tumor cells, leading to enhanced antitumor efficacy. This dual-responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug-release modality.}, number={17}, journal={ADVANCED MATERIALS}, author={Qian, Chenggen and Yu, Jicheng and Chen, Yulei and Hu, Quanyin and Xiao, Xuanzhong and Sun, Wujin and Wang, Chao and Feng, Peijian and Shen, Qun-Dong and Gu, Zhen}, year={2016}, month={May}, pages={3313–3320} }
 @misc{zhang_yu_bomba_zhu_gu_2016, title={Mechanical Force-Triggered Drug Delivery}, volume={116}, ISSN={["1520-6890"]}, DOI={10.1021/acs.chemrev.6b00369}, abstractNote={Advanced drug delivery systems (DDS) enhance treatment efficacy of different therapeutics in a dosage, spatial, and/or temporal controlled manner. To date, numerous chemical- or physical-based stimuli-responsive formulations or devices for controlled drug release have been developed. Among them, the emerging mechanical force-based stimulus offers a convenient and robust controlled drug release platform and has attracted increasing attention. The relevant DDS can be activated to promote drug release by different types of mechanical stimuli, including compressive force, tensile force, and shear force as well as indirect formats, remotely triggered by ultrasound and magnetic field. In this review, we provide an overview of recent advances in mechanically activated DDS. The opportunities and challenges regarding clinical translations are also discussed.}, number={19}, journal={CHEMICAL REVIEWS}, author={Zhang, Yuqi and Yu, Jicheng and Bomba, Hunter N. and Zhu, Yong and Gu, Zhen}, year={2016}, month={Oct}, pages={12536–12563} }
 @article{ye_yu_wang_nguyen_walker_buse_gu_2016, title={Microneedles Integrated with Pancreatic Cells and Synthetic Glucose-Signal Amplifiers for Smart Insulin Delivery}, volume={28}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201506025}, DOI={10.1002/adma.201506025}, abstractNote={An innovative microneedle (MN)-based cell therapy is developed for glucose-responsive regulation of the insulin secretion from exogenous pancreatic β-cells without implantation. One MN patch can quickly reduce the blood-sugar levels (BGLs) of chemically induced type-1 diabetic mice and stabilize BGLs at a reduced level for over 10 h.}, number={16}, journal={Advanced Materials}, publisher={Wiley}, author={Ye, Yanqi and Yu, Jicheng and Wang, Chao and Nguyen, Nhu-Y and Walker, Glenn M. and Buse, John B. and Gu, Zhen}, year={2016}, month={Mar}, pages={3115–3121} }
 @article{shi_xu_ye_song_cheng_di_hu_li_ju_jiang_et al._2016, title={Photo-Cross-Linked Scaffold with Kartogenin-Encapsulated Nanoparticles for Cartilage Regeneration}, volume={10}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b06663}, abstractNote={The regeneration of cartilage, an aneural and avascular tissue, is often compromised by its lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), a small molecular compound, can induce bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. The previous in vitro study showed that kartogenin also had a chondrogenesis effect on synovium derived mesenchymal stem cells (SMSCs). Herein, we present the effect of an ultraviolet-reactive, rapidly cross-linkable scaffold integrated with kartogenin-loaded nanoparticles using an innovational one-step technology. In vivo studies showed its potential role for cell homing, especially for recruiting the host's endogenous cells, including BMSCs and SMSCs, without cell transplantation. Of note, the regenerated tissues were close to the natural hyaline cartilage based on the histological tests, specific markers analysis, and biomechanical tests. This innovative KGN release system makes the chondrogenesis efficient and persistent.}, number={1}, journal={ACS NANO}, author={Shi, Dongquan and Xu, Xingquan and Ye, Yanqi and Song, Kai and Cheng, Yixiang and Di, Jin and Hu, Quanyin and Li, Jianxin and Ju, Huangxian and Jiang, Qing and et al.}, year={2016}, month={Jan}, pages={1292–1299} }
 @misc{hu_sun_wang_gu_2016, title={Recent advances of cocktail chemotherapy by combination drug delivery systems}, volume={98}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2015.10.022}, abstractNote={Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Hu, Quanyin and Sun, Wujin and Wang, Chao and Gu, Zhen}, year={2016}, month={Mar}, pages={19–34} }
 @article{yu_zhang_bomba_gu_2016, title={Stimuli-responsive delivery of therapeutics for diabetes treatment}, volume={1}, ISSN={2380-6761}, url={http://dx.doi.org/10.1002/BTM2.10036}, DOI={10.1002/BTM2.10036}, abstractNote={Abstract}, number={3}, journal={Bioengineering & Translational Medicine}, publisher={Wiley}, author={Yu, Jicheng and Zhang, Yuqi and Bomba, Hunter and Gu, Zhen}, year={2016}, month={Sep}, pages={323–337} }
 @article{ye_wang_hu_hochu_xin_wang_gu_2016, title={Synergistic Transcutaneous Immunotherapy Enhances Antitumor Immune Responses through Delivery of Checkpoint Inhibitors}, volume={10}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.6b04989}, abstractNote={Despite the promising efficacy of immunoregulation in cancer therapy, the clinical benefit has been restricted by inefficient infiltration of lymphocytes in the evolution of immune evasion. Also, immune-related adverse events have often occurred due to the off-target binding of therapeutics to normal tissues after systematic treatment. In light of this, we have developed a synergistic immunotherapy strategy that locally targets the immunoinhibitory receptor programmed cell death protein 1 (PD1) and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) for the treatment of melanoma through a microneedle-based transcutaneous delivery approach. The embedded immunotherapeutic nanocapsule loaded with anti-PD1 antibody (aPD1) is assembled from hyaluronic acid modified with 1-methyl-dl-tryptophan (1-MT), an inhibitor of IDO. This formulation method based on the combination strategy of "drug A in carriers formed by incorporation of drug B" facilitates the loading capacity of therapeutics. Moreover, the resulting delivery device elicits the sustained release and enhances retention of checkpoint inhibitors in the tumor microenvironment. Using a B16F10 mouse melanoma model, we demonstrate that this synergistic treatment has achieved potent antitumor efficacy, which is accompanied by enhanced effective T cell immunity as well as reduced immunosuppression in the local site.}, number={9}, journal={ACS NANO}, author={Ye, Yanqi and Wang, Jinqiang and Hu, Quanyin and Hochu, Gabrielle M. and Xin, Hongliang and Wang, Chao and Gu, Zhen}, year={2016}, month={Sep}, pages={8956–8963} }
 @article{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2016, title={Thrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation}, volume={29}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201604043}, DOI={10.1002/ADMA.201604043}, abstractNote={A thrombin-responsive closed-loop patch is developed for prolonged heparin delivery in a feedback-controlled manner. This microneedle-based patch can sense activated thrombin and subsequently releases heparin to prevent coagulation in the blood flow. This "smart" heparin patch can be transcutaneously inserted into skin without drug leakage and can sustainably regulate blood coagulation in response to thrombin.}, number={4}, journal={Advanced Materials}, publisher={Wiley}, author={Zhang, Yuqi and Yu, Jicheng and Wang, Jinqiang and Hanne, Nicholas J. and Cui, Zheng and Qian, Chenggen and Wang, Chao and Xin, Hongliang and Cole, Jacqueline H. and Gallippi, Caterina M. and et al.}, year={2016}, month={Nov}, pages={1604043} }
 @article{sun_ji_hu_yu_wang_qian_hochu_gu_2016, title={Transformable DNA nanocarriers for plasma membrane targeted delivery of cytokine}, volume={96}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2016.04.011}, abstractNote={Direct delivery of cytokines using nanocarriers holds great promise for cancer therapy. However, the nanometric scale of the vehicles made them susceptible to size-dependent endocytosis, reducing the plasma membrane-associated apoptosis signaling. Herein, we report a tumor microenvironment-responsive and transformable nanocarrier for cell membrane targeted delivery of cytokine. This formulation is comprised of a phospholipase A2 (PLA2) degradable liposome as a shell, and complementary DNA nanostructures (designated as nanoclews) decorated with cytokines as the cores. Utilizing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a model cytokine, we demonstrate that the TRAIL loaded DNA nanoclews are capable of transforming into nanofibers after PLA2 activation. The nanofibers with micro-scaled lengths efficiently present the loaded TRAIL to death receptors on the cancer cell membrane and amplified the apoptotic signaling with reduced TRAIL internalization.}, journal={BIOMATERIALS}, author={Sun, Wujin and Ji, Wenyan and Hu, Quanyin and Yu, Jicheng and Wang, Chao and Qian, Chenggen and Hochu, Gabrielle and Gu, Zhen}, year={2016}, month={Jul}, pages={1–10} }
 @article{hu_sun_lu_bomba_ye_jiang_isaacson_gu_2016, title={Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots}, volume={16}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.5b04343}, abstractNote={Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.}, number={2}, journal={NANO LETTERS}, author={Hu, Quanyin and Sun, Wujin and Lu, Yue and Bomba, Hunter N. and Ye, Yanqi and Jiang, Tianyue and Isaacson, Ari J. and Gu, Zhen}, year={2016}, month={Feb}, pages={1118–1126} }
 @article{mo_gu_2016, title={Tumor microenvironment and intracellular signal-activated nanomaterials for anticancer drug delivery}, volume={19}, ISSN={["1873-4103"]}, DOI={10.1016/j.mattod.2015.11.025}, abstractNote={Cancer-associated stimuli-responsive nanosystems have been increasingly considered for the delivery of anticancer drugs, which primarily target the tumor microenvironment and/or intracellular elements to enhance intratumoral accumulation and promote drug release at the target site. The signals facilitating drug delivery include tumor and endocytic acidities, hypoxia, enzyme overexpression, as well as high levels of intracellular glutathione, reactive oxygen species, and adenosine-5′-triphosphate. This article reviews the current techniques and ongoing developments in anticancer drug delivery using these signals. In particular, the focus is placed on design strategies and methods of formulating novel nanoscaled materials. The merits and drawbacks of recent strategies, as well as potential future developments, are discussed.}, number={5}, journal={MATERIALS TODAY}, author={Mo, Ran and Gu, Zhen}, year={2016}, month={Jun}, pages={274–283} }
 @article{ye_yu_gu_2016, title={Versatile Protein Nanogels Prepared by In Situ Polymerization}, volume={217}, ISSN={["1521-3935"]}, DOI={10.1002/macp.201500296}, abstractNote={Proteins with unique structure and function have tremendous applications for cancer treatment, vaccination, diagnosis, regenerative medicine, and therapies for loss‐of‐function genetic diseases. A general method of loading and delivering active forms of proteins toward cells and tissues is highly desirable for remaining activity, enhancing stability, and avoiding potential immunogenicity of proteins. Nanogels with cross‐linked structure provide a versatile platform for storage and release of proteins. Herein, the recent advances in protein nanogels made by the in situ polymerization method, from preparation to application are summarized. A range of stimuli‐responsive formulations for on‐demand release, in a spatial, temporal, and dosage‐controlled manner, is highlighted. Future opportunities as well as challenges of protein nanogels are also discussed.
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}, number={3}, journal={MACROMOLECULAR CHEMISTRY AND PHYSICS}, author={Ye, Yanqi and Yu, Jicheng and Gu, Zhen}, year={2016}, month={Feb}, pages={333–343} }
 @article{pacardo_neupane_rikard_lu_mo_mishra_tracy_wang_ligler_gu_2015, title={A dual wavelength-activatable gold nanorod complex for synergistic cancer treatment}, volume={7}, ISSN={["2040-3372"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000357805700034&KeyUID=WOS:000357805700034}, DOI={10.1039/c5nr01568e}, abstractNote={A multifunctional gold nanorod complex was formulated for synergistic anticancer treatment upon ultraviolet (UV) and infrared (IR) light dual irradiations.}, number={28}, journal={NANOSCALE}, author={Pacardo, Dennis B. and Neupane, Bhanu and Rikard, S. Michaela and Lu, Yue and Mo, Ran and Mishra, Sumeet R. and Tracy, Joseph B. and Wang, Gufeng and Ligler, Frances S. and Gu, Zhen}, year={2015}, pages={12096–12103} }
 @article{pacardo_neupane_wang_gu_walker_ligler_2015, title={A temperature microsensor for measuring laser-induced heating in gold nanorods}, volume={407}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-014-8222-9}, abstractNote={Measuring temperature is an extensively explored field of analysis, but measuring a temperature change in a nanoparticle is a new challenge. Here, a microsensor is configured to measure temperature changes in gold nanorods in solution upon laser irradiation. The device consists of a silicon wafer coated with silicon nitride in which a microfabricated resistance temperature detector was embedded and attached to a digital multimeter. A polydimethylsiloxane mold served as a microcontainer for the sample attached on top of the silicon membrane. This enables laser irradiation of the gold nanorods and subsequent measurement of temperature changes. The results showed a temperature increase of 8 to 10 °C and good correlation with theoretical calculations and bulk sample direct temperature measurements. These results demonstrate the suitability of this simple temperature microsensor for determining laser-induced heating profiles of metallic nanomaterials; such measurements will be essential for optimizing therapeutic and catalytic applications.}, number={3}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Pacardo, Dennis B. and Neupane, Bhanu and Wang, Gufeng and Gu, Zhen and Walker, Glenn M. and Ligler, Frances S.}, year={2015}, month={Jan}, pages={719–725} }
 @article{mo_jiang_sun_gu_2015, title={ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery}, volume={50}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2015.01.053}, abstractNote={Stimuli-triggered drug delivery systems are primarily focused on the applications of the tumor microenvironmental or cellular physiological cues to enhance the release of drugs at the target site. In this study, we applied adenosine-5′-triphosphate (ATP), the primary “energy molecule”, as a trigger for enhanced release of preloaded drugs responding to the intracellular ATP concentration that is significantly higher than the extracellular level. A new ATP-responsive anticancer drug delivery strategy utilizing DNA-graphene crosslinked hybrid nanoaggregates as carriers was developed for controlled release of doxorubicin (DOX), which consists of graphene oxide (GO), two single-stranded DNA (ssDNA, denoted as DNA1 and DNA2) and ATP aptamer. The single-stranded DNA1 and DNA2 together with the ATP aptamer serve as the linkers upon hybridization for controlled assembly of the DNA-GO nanoaggregates, which effectively inhibited the release of DOX from the GO nanosheets. In the presence of ATP, the responsive formation of the ATP/ATP aptamer complex causes the dissociation of the aggregates, which promoted the release of DOX in the environment with a high ATP concentration such as cytosol compared with that in the ATP-deficient extracellular fluid. This supports the development of a novel ATP-responsive platform for targeted on-demand delivery of anticancer drugs inside specific cells.}, journal={BIOMATERIALS}, author={Mo, Ran and Jiang, Tianyue and Sun, Wujin and Gu, Zhen}, year={2015}, month={May}, pages={67–74} }
 @article{mitragotri_anderson_chen_chow_ho_kabanov_karp_kataoka_mirkin_petrosko_et al._2015, title={Accelerating the Translation of Nanomaterials in Biomedicine}, volume={9}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b03569}, abstractNote={Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples.}, number={7}, journal={ACS NANO}, author={Mitragotri, Samir and Anderson, Daniel G. and Chen, Xiaoyuan and Chow, Edward K. and Ho, Dean and Kabanov, Alexander V. and Karp, Jeffrey M. and Kataoka, Kazunori and Mirkin, Chad A. and Petrosko, Sarah Hurst and et al.}, year={2015}, month={Jul}, pages={6644–6654} }
 @article{hu_sun_qian_wang_bomba_gu_2015, title={Anticancer Platelet-Mimicking Nanovehicles}, volume={27}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201503323}, abstractNote={A core-shell nanovehicle coated with a platelet membrane (PM) is developed for targeted and site-specific delivery of an extracellularly active drug and an intracellular functional small-molecular drug, leading to enhanced antitumor efficacy. This PM-coated nanovehicle can also effectively eliminate the circulating tumor cells in vivo and inhibit development of tumor metastasis.}, number={44}, journal={ADVANCED MATERIALS}, author={Hu, Quanyin and Sun, Wujin and Qian, Chengen and Wang, Chao and Bomba, Hunter N. and Gu, Zhen}, year={2015}, month={Nov}, pages={7043-+} }
 @article{ji_sun_feng_song_zhang_ouyang_gu_xie_2015, title={Characterization of a novel N-acetylneuraminic acid lyase favoring N-acetylneuraminic acid synthesis}, volume={5}, ISSN={["2045-2322"]}, DOI={10.1038/srep09341}, abstractNote={Abstract}, journal={SCIENTIFIC REPORTS}, author={Ji, Wenyan and Sun, Wujin and Feng, Jinmei and Song, Tianshun and Zhang, Dalu and Ouyang, Pingkai and Gu, Zhen and Xie, Jingjing}, year={2015}, month={Mar} }
 @article{xiao-hui_ji-cheng_nai-yan_wei-dong_yu-yan_zhen_2015, title={Confinement-induced nanocrystal alignment of conjugated polymer by the soft-stamped nanoimprint lithography}, volume={24}, ISSN={["1741-4199"]}, DOI={10.1088/1674-1056/24/10/104215}, abstractNote={Soft-stamped nanoimprint lithography (NIL) is considered as one of the most effective processes of nanoscale patterning because of its low cost and high throughput. In this work, this method is used to emboss the poly (9, 9-dioctylfluorene) film. By reducing the linewidth of the nanogratings on the stamp, the orientations of nanocrystals are confined along the grating vector in the nanoimprint process, where the confinement linewidth is comparable to the geometrical size of the nanocrystal. When the linewidth is about 400 nm, the poly (9, 9-dioctylfluorene) (PFO) nanocrystals could be orderly arranged in the nanogratings, so that both pattern transfer and well-aligned nanocrystal arrangement could be achieved in a single step by the soft-stamped NIL. The relevant mechanism of the nanocrystalline alignment in these nanogratings is fully discussed. The modulation of nanocrystal alignment is of benefit to the charge mobilities and other performances of PFO-based devices for the future applications.}, number={10}, journal={CHINESE PHYSICS B}, author={Xiao-Hui, Li and Ji-Cheng, Yu and Nai-Yan, Lu and Wei-Dong, Zhang and Yu-Yan, Weng and Zhen, Gu}, year={2015}, month={Oct} }
 @article{sun_ji_hall_hu_wang_beisel_gu_2015, title={Cover Picture: Self-Assembled DNA Nanoclews for the Efficient Delivery of CRISPR-Cas9 for Genome Editing (Angew. Chem. Int. Ed. 41/2015)}, volume={54}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/ANIE.201508399}, DOI={10.1002/ANIE.201508399}, abstractNote={A biologically inspired carrier for the delivery of CRISPR–Cas9 that is based on yarn-like DNA nanoparticles, so-called DNA nanoclews, is described by Z. Gu, C. L. Beisel, and co-workers in their Communication on page 12029 ff. DNA nanoclews (the flying saucers), partially complementary to the single guide RNA (sgRNA), were efficiently loaded with Cas9/sgRNA complexes (the missiles) and delivered the complexes into human cells for genome editing. A biologically inspired carrier for the delivery of CRISPR–Cas9 that is based on yarn-like DNA nanoparticles, so-called DNA nanoclews, is described by Z. Gu, C. L. Beisel, and co-workers in their Communication on page 12029 ff. DNA nanoclews (the flying saucers), partially complementary to the single guide RNA (sgRNA), were efficiently loaded with Cas9/sgRNA complexes (the missiles) and delivered the complexes into human cells for genome editing. Propylene Epoxidation Catalysts Main Group Chemistry}, number={41}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Sun, Wujin and Ji, Wenyan and Hall, Jordan M. and Hu, Quanyin and Wang, Chao and Beisel, Chase L. and Gu, Zhen}, year={2015}, month={Sep}, pages={11877–11877} }
 @article{jiang_sun_zhu_burns_khan_mo_gu_2015, title={Drug Delivery: Furin-Mediated Sequential Delivery of Anticancer Cytokine and Small-Molecule Drug Shuttled by Graphene (Adv. Mater. 6/2015)}, volume={27}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201570035}, DOI={10.1002/ADMA.201570035}, abstractNote={A cellular protease-mediated graphene-based nanosystem is developed on page 1021 by R. Mo, Z. Gu, and co-workers for the co-delivery of a membrane-associated cytokine (tumor-necrosis-factor-related apoptosisinducing ligand, TRAIL) and an intracellular-acting small-molecule drug (Doxorubicin, DOX). TRAIL and DOX can be sequentially released toward the plasma membrane and nucleus, respectively.}, number={6}, journal={Advanced Materials}, publisher={Wiley}, author={Jiang, Tianyue and Sun, Wujin and Zhu, Qiuwen and Burns, Nancy A. and Khan, Saad A. and Mo, Ran and Gu, Zhen}, year={2015}, month={Feb}, pages={958–958} }
 @misc{sun_gu_2015, title={Engineering DNA scaffolds for delivery of anticancer therapeutics}, volume={3}, ISSN={["2047-4849"]}, DOI={10.1039/c4bm00459k}, abstractNote={DNA scaffolds with programmability in size, shape and surface chemistry have been engineered for the delivery of various anticancer therapeutics.}, number={7}, journal={BIOMATERIALS SCIENCE}, author={Sun, Wujin and Gu, Zhen}, year={2015}, pages={1018–1024} }
 @article{di_yu_ye_ranson_jindal_gu_2015, title={Engineering Synthetic Insulin-Secreting Cells Using Hyaluronic Acid Microgels Integrated with Glucose-Responsive Nanoparticles}, volume={8}, ISSN={["1865-5033"]}, DOI={10.1007/s12195-015-0390-y}, number={3}, journal={CELLULAR AND MOLECULAR BIOENGINEERING}, author={Di, Jin and Yu, Jicheng and Ye, Yanqi and Ranson, Davis and Jindal, Abhilasha and Gu, Zhen}, year={2015}, month={Sep}, pages={445–454} }
 @misc{zhang_yu_shen_gu_2015, title={Glucose-responsive synthetic closed-loop insulin delivery systems}, volume={27}, number={1}, journal={Progress in Chemistry}, author={Zhang, Y. Q. and Yu, J. C. and Shen, Q. D. and Gu, Z.}, year={2015}, pages={11–26} }
 @article{chen_nan_lu_wang_chu_gu_2015, title={Hybrid Fe3O4-Poly(acrylic acid) Nanogels for Theranostic Cancer Treatment}, volume={11}, ISSN={["1550-7041"]}, DOI={10.1166/jbn.2015.2001}, abstractNote={Multifunctional nanomedicine integrated with both therapy and diagnostics holds vast potential in cancer treatment. We developed hybrid Fe3O4-poly(acrylic acid) (PAA) nanogels for both drug delivery and magnetic resonance imaging (MRI). Superparamagnetic Fe3O4 nanoparticles were encapsulated inside porous PAA nanogels via an in situ co-precipitation approach. With successive growth of magnetic nanoparticles, the highest magnetization saturation (M(s)) value of the Fe3O4 nanoparticles in the PAA nanogels was determined as 20 emu/g. The resulting hybrid Fe3O4-PAA nanogels showed high drug loading capacity (98%) and sustained drug release in vitro. Cytotoxicity assays and cellular imaging demonstrated that the hybrid nanogels were highly biocompatible and efficiently internalized in human neuroblastoma SH-SY5Y cells. In MRI studies, the hybrid nanogels exhibited an excellent contrast in T2 weighted imaging and a high MRI sensitivity in the tumor site.}, number={5}, journal={JOURNAL OF BIOMEDICAL NANOTECHNOLOGY}, author={Chen, Ying and Nan, Jingya and Lu, Yue and Wang, Chunpeng and Chu, Fuxiang and Gu, Zhen}, year={2015}, month={May}, pages={771–779} }
 @article{yu_zhang_ye_disanto_sun_ranson_ligler_buse_gu_2015, title={Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery}, volume={112}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1505405112}, abstractNote={Significance}, number={27}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Yu, Jicheng and Zhang, Yuqi and Ye, Yanqi and DiSanto, Rocco and Sun, Wujin and Ranson, Davis and Ligler, Frances S. and Buse, John B. and Gu, Zhen}, year={2015}, month={Jul}, pages={8260–8265} }
 @article{hu_sun_qian_wang_bomba_gu_2015, title={Nanomedicine: Anticancer Platelet-Mimicking Nanovehicles (Adv. Mater. 44/2015)}, volume={27}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201570298}, DOI={10.1002/ADMA.201570298}, abstractNote={The inside front cover is a schematic representation of an anticancer platelet-mimicking drug-delivery system described by Z. Gu and co-workers on page 7043. The platelet membrane-coated nanovehicles can inhibit primary tumor growth, and also eliminate circulating tumor cells through sequential delivery of plasma membrane-associated cytokine and intracellularly functional small-molecule drugs.}, number={44}, journal={Advanced Materials}, publisher={Wiley}, author={Hu, Quanyin and Sun, Wujin and Qian, Chengen and Wang, Chao and Bomba, Hunter N. and Gu, Zhen}, year={2015}, month={Nov}, pages={7014–7014} }
 @article{yan_li_kunecke_gu_guo_2015, title={Polypyrrole-Based Implantable Electroactive Pump for Controlled Drug Microinjection}, volume={7}, ISSN={["1944-8244"]}, DOI={10.1021/acsami.5b04551}, abstractNote={Implantable devices for long-lasting controlled insulin microinjection are of great value to diabetic patients. To address this need, we develop a flexible electroactive pump based on a biocompatible polypyrrole composite film that comprises a polypyrrole matrix and a macromolecular dopant of polycaprolactone-block-polytetrahydrofuran-block-polycaprolactone. Using phosphate-buffered saline as the electrolyte, this film demonstrates much higher electroactivity and reproducibility than conventional Cl--doped polypyrrole, making it an excellent actuator for driving an implantable pump. At a driving current density of 1 mA/cm2, the pump demonstrates a consistent output capacity of 10.5 at 0.35 μL/s over 20 cycles. This work paves the way for the development of an implantable electroactive pump to improve the quality of life of diabetics.}, number={27}, journal={ACS APPLIED MATERIALS & INTERFACES}, author={Yan, Bingxi and Li, Boyi and Kunecke, Forest and Gu, Zhen and Guo, Liang}, year={2015}, month={Jul}, pages={14563–14568} }
 @misc{pacardo_ligler_gu_2015, title={Programmable nanomedicine: synergistic and sequential drug delivery systems}, volume={7}, ISSN={["2040-3372"]}, DOI={10.1039/c4nr07677j}, abstractNote={Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.}, number={8}, journal={NANOSCALE}, author={Pacardo, Dennis B. and Ligler, Frances S. and Gu, Zhen}, year={2015}, pages={3381–3391} }
 @misc{disanto_subramanian_gu_2015, title={Recent advances in nanotechnology for diabetes treatment}, volume={7}, ISSN={["1939-0041"]}, DOI={10.1002/wnan.1329}, abstractNote={Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to ‘closed‐loop’ insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels (BGLs). ‘Closing the loop’ between BGL measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. WIREs Nanomed Nanobiotechnol 2015, 7:548–564. doi: 10.1002/wnan.1329}, number={4}, journal={WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY}, author={DiSanto, Rocco Michael and Subramanian, Vinayak and Gu, Zhen}, year={2015}, pages={548–564} }
 @article{sun_ji_hall_hu_wang_beisel_gu_2015, title={Self-Assembled DNA Nanoclews for the Efficient Delivery of CRISPR-Cas9 for Genome Editing}, volume={54}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/ANIE.201506030}, DOI={10.1002/anie.201506030}, abstractNote={Abstract}, number={41}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Sun, Wujin and Ji, Wenyan and Hall, Jordan M. and Hu, Quanyin and Wang, Chao and Beisel, Chase L. and Gu, Zhen}, year={2015}, month={Aug}, pages={12029–12033} }
 @article{di_kim_hu_jiang_gu_2015, title={Spatiotemporal drug delivery using laser-generated-focused ultrasound system}, volume={220}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2015.08.033}, abstractNote={Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Di, Jin and Kim, Jinwook and Hu, Quanyin and Jiang, Xiaoning and Gu, Zhen}, year={2015}, month={Dec}, pages={592–599} }
 @article{di_yao_ye_cui_yu_ghosh_zhu_gu_2015, title={Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots}, volume={9}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b03975}, abstractNote={Mechanical force-based stimulus provides a simple and easily accessible manner for spatiotemporally controlled drug delivery. Here we describe a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles. By applying a tensile strain to the elastomer film, the release of drug from the microdepot is promoted due to the enlarged surface area for diffusion and Poisson's ratio-induced compression on the microdepot. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. Our work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from microdepots for anticancer and antibacterial treatments. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically induced type 1 diabetic mice.}, number={9}, journal={ACS NANO}, author={Di, Jin and Yao, Shanshan and Ye, Yanqi and Cui, Zheng and Yu, Jicheng and Ghosh, Tushar K. and Zhu, Yong and Gu, Zhen}, year={2015}, month={Sep}, pages={9407–9415} }
 @article{lu_hu_lin_pacardo_wang_sun_ligler_dickey_gu_2015, title={Transformable liquid-metal nanomedicine}, volume={6}, ISSN={["2041-1723"]}, DOI={10.1038/ncomms10066}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, publisher={Springer Nature}, author={Lu, Yue and Hu, Quanyin and Lin, Yiliang and Pacardo, Dennis B. and Wang, Chao and Sun, Wujin and Ligler, Frances S. and Dickey, Michael D. and Gu, Zhen}, year={2015}, month={Dec} }
 @article{mo_jiang_disanto_tai_gu_2014, title={ATP-triggered anticancer drug delivery}, volume={5}, ISSN={["2041-1723"]}, DOI={10.1038/ncomms4364}, abstractNote={Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.}, journal={NATURE COMMUNICATIONS}, author={Mo, Ran and Jiang, Tianyue and DiSanto, Rocco and Tai, Wanyi and Gu, Zhen}, year={2014}, month={Mar} }
 @article{sun_lu_gu_2014, title={Advances in Anticancer Protein Delivery using Micro-/Nanoparticles}, volume={31}, ISSN={["1521-4117"]}, DOI={10.1002/ppsc.201400140}, abstractNote={Proteins exhibiting anticancer activities, especially those capable of discriminately killing cancer cells, have attracted increasing interest in developing protein‐based anticancer therapeutics. This Progress Report surveys recent advances in delivering anticancer proteins directly to tumor tissue for inducing apoptosis/necrosis or indirectly to antigen presenting cells for provoking immune responses. Protein delivery carriers such as inorganic particles, lipid particles, polymeric particles, DNA/protein‐based biomacromolecular particles, as well as cell based carriers are reviewed with comments on their advantages and limitations. Future challenges and opportunities are also discussed.}, number={12}, journal={PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION}, author={Sun, Wujin and Lu, Yue and Gu, Zhen}, year={2014}, month={Dec}, pages={1204–1222} }
 @article{tai_mo_di_subramanian_gu_buse_gu_2014, title={Bio-lnspired Synthetic Nanovesicles for Glucose-Responsive Release of Insulin}, volume={15}, ISSN={["1526-4602"]}, DOI={10.1021/bm500364a}, abstractNote={A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days.}, number={10}, journal={BIOMACROMOLECULES}, author={Tai, Wanyi and Mo, Ran and Di, Jin and Subramanian, Vinayak and Gu, Xiao and Buse, John B. and Gu, Zhen}, year={2014}, month={Oct}, pages={3495–3502} }
 @article{zhao_liu_hsieh_wang_tai_joo_wang_gu_tang_2014, title={Clickable Protein Nanocapsules for Targeted Delivery of Recombinant p53 Protein}, volume={136}, ISSN={["0002-7863"]}, DOI={10.1021/ja508083g}, abstractNote={Encapsulating anticancer protein therapeutics in nanocarriers is an attractive option to minimize active drug destruction, increase local accumulation at the disease site, and decrease side effects to other tissues. Tumor-specific ligands can further facilitate targeting the nanocarriers to tumor cells and reduce nonspecific cellular internalization. Rationally designed non-covalent protein nanocapsules incorporating copper-free "click chemistry" moieties, polyethylene glycol (PEG) units, redox-sensitive cross-linker, and tumor-specific targeting ligands were synthesized to selectively deliver intracellular protein therapeutics into tumor cells via receptor-mediated endocytosis. These nanocapsules can be conjugated to different targeting ligands of choice, such as anti-Her2 antibody single-chain variable fragment (scFv) and luteinizing hormone releasing hormone (LHRH) peptide, resulting in specific and efficient accumulation within tumor cells overexpressing corresponding receptors. LHRH-conjugated nanocapsules selectively delivered recombinant human tumor suppressor protein p53 and its tumor-selective supervariant into targeted tumor cells, which led to reactivation of p53-mediated apoptosis. Our results validate a general approach for targeted protein delivery into tumor cells using cellular-responsive nanocarriers, opening up new opportunities for the development of intracellular protein-based anticancer treatment.}, number={43}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Zhao, Muxun and Liu, Yarong and Hsieh, Renee S. and Wang, Nova and Tai, Wanyi and Joo, Kye-Il and Wang, Pin and Gu, Zhen and Tang, Yi}, year={2014}, month={Oct}, pages={15319–15325} }
 @article{sun_jiang_lu_reiff_mo_gu_2014, title={Cocoon-Like Self-Degradable DNA Nanoclew for Anticancer Drug Delivery}, volume={136}, ISSN={["0002-7863"]}, DOI={10.1021/ja5088024}, abstractNote={A bioinspired cocoon-like anticancer drug delivery system consisting of a deoxyribonuclease (DNase)-degradable DNA nanoclew (NCl) embedded with an acid-responsive DNase I nanocapsule (NCa) was developed for targeted cancer treatment. The NCl was assembled from a long-chain single-stranded DNA synthesized by rolling-circle amplification (RCA). Multiple GC-pair sequences were integrated into the NCl for enhanced loading capacity of the anticancer drug doxorubicin (DOX). Meanwhile, negatively charged DNase I was encapsulated in a positively charged acid-degradable polymeric nanogel to facilitate decoration of DNase I into the NCl by electrostatic interactions. In an acidic environment, the activity of DNase I was activated through the acid-triggered shedding of the polymeric shell of the NCa, resulting in the cocoon-like self-degradation of the NCl and promoting the release of DOX for enhanced therapeutic efficacy.}, number={42}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Sun, Wujin and Jiang, Tianyue and Lu, Yue and Reiff, Margaret and Mo, Ran and Gu, Zhen}, year={2014}, month={Oct}, pages={14722–14725} }
 @article{jiang_mo_bellotti_zhou_gu_2014, title={Drug Delivery: Gel-Liposome-Mediated Co-Delivery of Anticancer Membrane-Associated Proteins and Small-Molecule Drugs for Enhanced Therapeutic Efficacy (Adv. Funct. Mater. 16/2014)}, volume={24}, ISSN={1616-301X}, url={http://dx.doi.org/10.1002/ADFM.201470099}, DOI={10.1002/ADFM.201470099}, abstractNote={Sequential and site-specific co-delivery of two anticancer therapeutics in a programmed manner is demonstrated by J. Zhou, Z. Gu, and co-workers on page 2295. The delivery is triggered by the tumor microenvironment and cellular conditions. The gel-liposome based nanovehicle can transport and release an anticancer cytokine (TRAIL) and small-molecule drug (doxorubicin) to their distinct acting sites: the cellular membrane and nucleus, respectively.}, number={16}, journal={Advanced Functional Materials}, publisher={Wiley}, author={Jiang, Tianyue and Mo, Ran and Bellotti, Adriano and Zhou, Jianping and Gu, Zhen}, year={2014}, month={Apr}, pages={2258–2258} }
 @article{di_price_gu_jiang_jing_gu_2014, title={Drug Delivery: Ultrasound-Triggered Regulation of Blood Glucose Levels Using Injectable Nano-Network (Adv. Healthcare Mater. 6/2014)}, volume={3}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201470027}, DOI={10.1002/ADHM.201470027}, abstractNote={On page 811, Y. Jing, Z. Gu and co-workers present the integration of an injectable nano-network with a focused ultrasound system (FUS) which can remotely regulate insulin release both in vitro and in vivo. Serving as a synthetic insulin reservoir, the nano-network consisting of adhesive biodegradable nanoparticles promotes insulin release upon FUS triggers in a pulsatile, remote and non-invasive control manner. Image courtesy of Dwayne Martin.}, number={6}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Di, Jin and Price, Jennifer and Gu, Xiao and Jiang, Xiaoning and Jing, Yun and Gu, Zhen}, year={2014}, month={Jun}, pages={789–789} }
 @misc{mo_jiang_di_tai_gu_2014, title={Emerging micro-and nanotechnology based synthetic approaches for insulin delivery}, volume={43}, ISSN={["1460-4744"]}, DOI={10.1039/c3cs60436e}, abstractNote={Insulin is essential for type 1 and advanced type 2 diabetics to maintain blood glucose levels and prolong lives. The traditional administration requires frequent subcutaneous insulin injections that are associated with poor patient compliance, including pain, local tissue necrosis, infection, and nerve damage. Taking advantage of emerging micro- and nanotechnologies, numerous alternative strategies integrated with chemical approaches for insulin delivery have been investigated. This review outlines recent developments in the controlled delivery of insulin, including oral, nasal, pulmonary, transdermal, subcutaneous and closed-loop insulin delivery. Perspectives from new materials, formulations and devices at the micro- or nano-scales are specifically surveyed. Advantages and limitations of current delivery methods, as well as future opportunities and challenges are also discussed.}, number={10}, journal={CHEMICAL SOCIETY REVIEWS}, author={Mo, Ran and Jiang, Tianyue and Di, Jin and Tai, Wanyi and Gu, Zhen}, year={2014}, pages={3595–3629} }
 @article{mo_jiang_gu_2014, title={Enhanced Anticancer Efficacy by ATP-Mediated Liposomal Drug Delivery}, volume={53}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201400268}, abstractNote={Abstract}, number={23}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Mo, Ran and Jiang, Tianyue and Gu, Zhen}, year={2014}, month={Jun}, pages={5815–5820} }
 @article{hu_katti_gu_2014, title={Enzyme-responsive nanomaterials for controlled drug delivery}, volume={6}, ISSN={["2040-3372"]}, DOI={10.1039/c4nr04249b}, abstractNote={Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.}, number={21}, journal={NANOSCALE}, author={Hu, Quanyin and Katti, Prateek S. and Gu, Zhen}, year={2014}, pages={12273–12286} }
 @article{tai_mo_lu_jiang_gu_2014, title={Folding graft copolymer with pendant drug segments for co-delivery of anticancer drugs}, volume={35}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2014.05.004}, abstractNote={A graft copolymer with pendant drug segments can fold into nanostructures in a protein folding-like manner. The graft copolymer is constructed by directly polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu(CPT)-NCA) on multiple sites of poly(ethylene glycol) (PEG)-based main chain via the ring open polymerization (ROP). The "purely" conjugated anticancer agent camptothecin (CPT) is hydrophobic and serves as the principal driving force during the folding process. When exposed to water, the obtained copolymer, together with doxorubicin (Dox), another anticancer agent, can fold into monodispersed nanocarriers (with a diameter of around 50 nm) for dual-drug delivery. Equipped with a PEG shell, the nanocarriers displayed good stability and can be internalized by a variety of cancer cell lines via the lipid raft and clathrin-mediated endocytotic pathway without premature leakage, which showed a high synergetic activity of CPT and Dox toward various cancer cells. In vivo study validated that the nanocarriers exhibited strong accumulation in tumor sites and showed a prominent anticancer activity against the lung cancer xenograft mice model compared with free drugs.}, number={25}, journal={BIOMATERIALS}, author={Tai, Wanyi and Mo, Ran and Lu, Yue and Jiang, Tianyue and Gu, Zhen}, year={2014}, month={Aug}, pages={7194–7203} }
 @article{jiang_sun_zhu_burns_khan_mo_gu_2014, title={Furin-Mediated Sequential Delivery of Anticancer Cytokine and Small-Molecule Drug Shuttled by Graphene}, volume={27}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201404498}, DOI={10.1002/ADMA.201404498}, abstractNote={A cellular protease (furin)-mediated graphene-based nanosystem is developed for co-delivery of a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand, TRAIL) and an intracellular-acting small-molecule drug (Doxorubicin, DOX). TRAIL and DOX can be sequentially released toward the plasma membrane and nucleus, respectively.}, number={6}, journal={Advanced Materials}, publisher={Wiley}, author={Jiang, Tianyue and Sun, Wujin and Zhu, Qiuwen and Burns, Nancy A. and Khan, Saad A. and Mo, Ran and Gu, Zhen}, year={2014}, month={Dec}, pages={1021–1028} }
 @article{dong_eltoukhy_alabi_khan_veiseh_dorkin_sirirungruang_yin_tang_pelet_et al._2014, title={Lipid-Like Nanomaterials for Simultaneous Gene Expression and Silencing In Vivo}, volume={3}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201400054}, DOI={10.1002/ADHM.201400054}, abstractNote={New lipid-like nanomaterials are developed to simultaneously regulate expression of multiple genes. Self-assembled nanoparticles are capable of efficiently encapsulating pDNA and siRNA. These nanoparticles are shown to induce simultaneous gene expression and silencing both in vitro and in vivo.}, number={9}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Dong, Yizhou and Eltoukhy, Ahmed A. and Alabi, Christopher A. and Khan, Omar F. and Veiseh, Omid and Dorkin, J. Robert and Sirirungruang, Sasilada and Yin, Hao and Tang, Benjamin C. and Pelet, Jeisa M. and et al.}, year={2014}, month={Mar}, pages={1392–1397} }
 @article{jiang_mo_bellotti_zhou_gu_2014, title={Molecule Drugs for Enhanced Therapeutic Efficacy}, volume={24}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.201303222}, abstractNote={A programmed drug‐delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core–shell‐based “nanodepot” consisting of a liposomal core and a crosslinked‐gel shell (designated Gelipo) is developed for the sequential and site‐specific delivery (SSSD) of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and doxorubicin (Dox). As a small‐molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half‐maximal inhibitory concentration (IC50) of TRAIL and Dox co‐loaded Gelipo (TRAIL/Dox‐Gelipo) toward human breast cancer (MDA‐MB‐231) cells is 83 ng mL–1 (Dox concentration), which presents a 5.9‐fold increase in the cytotoxicity compared to 569 ng mL–1 of Dox‐loaded Gelipo (Dox‐Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA‐MB‐231 xenograft tumor animal model.}, number={16}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Jiang, Tianyue and Mo, Ran and Bellotti, Adriano and Zhou, Jianping and Gu, Zhen}, year={2014}, month={Apr}, pages={2295–2304} }
 @article{mo_jiang_gu_2014, title={Recent progress in multidrug delivery to cancer cells by liposomes}, volume={9}, ISSN={["1748-6963"]}, DOI={10.2217/nnm.14.62}, abstractNote={NanomedicineVol. 9, No. 8 EditorialRecent progress in multidrug delivery to cancer cells by liposomesRan Mo, Tianyue Jiang & Zhen GuRan MoJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USAMolecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaSearch for more papers by this author, Tianyue JiangJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USAMolecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAState Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, ChinaSearch for more papers by this author & Zhen GuAuthor for correspondence: E-mail Address: zgu@email.unc.eduJoint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USAMolecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USASearch for more papers by this authorPublished Online:14 Aug 2014https://doi.org/10.2217/nnm.14.62AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: chemotherapyco-deliverycombination cancer therapydrug deliverygene therapyliposomeprotein therapyReferences1 Bangham AD, Standish MM, Watkins JC et al. 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cells1 January 2015 | Journal of Materials Chemistry B, Vol. 3, No. 8 Vol. 9, No. 8 STAY CONNECTED Metrics Downloaded 458 times History Published online 14 August 2014 Published in print June 2014 Information© Future Medicine LtdKeywordschemotherapyco-deliverycombination cancer therapydrug deliverygene therapyliposomeprotein therapyFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download}, number={8}, journal={NANOMEDICINE}, author={Mo, Ran and Jiang, Tianyue and Gu, Zhen}, year={2014}, month={Jun}, pages={1117–1120} }
 @article{lu_mo_tai_sun_pacardo_qian_shen_ligler_gu_2014, title={Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc07004f}, abstractNote={Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.}, number={95}, journal={CHEMICAL COMMUNICATIONS}, author={Lu, Yue and Mo, Ran and Tai, Wanyi and Sun, Wujin and Pacardo, Dennis B. and Qian, Chenggen and Shen, Qundong and Ligler, Frances S. and Gu, Zhen}, year={2014}, pages={15105–15108} }
 @misc{lu_sun_gu_2014, title={Stimuli-responsive nanomaterials for therapeutic protein delivery}, volume={194}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2014.08.015}, abstractNote={Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Lu, Yue and Sun, Wujin and Gu, Zhen}, year={2014}, month={Nov}, pages={1–19} }
 @article{yu_chen_zhang_yao_cheng-gen_huang_zhu_jiang_shen_gu_2014, title={pH-Responsive and near-infrared-emissive polymer nanoparticles for simultaneous delivery, release, and fluorescence tracking of doxorubicin in vivo}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c3cc49870k}, abstractNote={Dextran modified with pendant acetals is used to load doxorubicin (DOX) and a near-infrared-emissive conjugated polymer (BTTPF), and this aims to provide selective drug release at therapeutic targets including tumors. The BTTPF is applicable to tracking the anticancer drug release through the change of Förster resonance energy transfer efficiency between doxorubicin and BTTPF during degradation of the nanoparticles in vivo.}, number={36}, journal={CHEMICAL COMMUNICATIONS}, author={Yu, Ji-Cheng and Chen, Yu-Lei and Zhang, Yu-Qi and Yao, Xi-Kuang and Cheng-Gen, Qian and Huang, Jun and Zhu, Sha and Jiang, Xi-Qun and Shen, Qun-Dong and Gu, Zhen}, year={2014}, pages={4699–4702} }
 @article{zhao_hu_gu_joo_wang_tang_2013, title={Degradable polymeric nanocapsule for efficient intracellular delivery of a high molecular weight tumor-selective protein complex}, volume={8}, ISSN={1748-0132}, url={http://dx.doi.org/10.1016/j.nantod.2012.12.003}, DOI={10.1016/j.nantod.2012.12.003}, abstractNote={The development of stimuli-responsive, nano-scale therapeutics that selectively target and attack tumors is a major research focus in cancer nanotechnology. A potent therapeutic option is to directly arming the cancer cells with apoptotic-inducing proteins that are not affected by tumoral anti-apoptotic maneuvers. The avian virus-derived apoptin forms a high-molecular weight protein complex that selectively accumulates in the nucleus of cancer cell to induce apoptotic cell death. To achieve the efficient intracellular delivery of this tumor-selective protein in functional form, we synthesized degradable, sub-100 nm, core–shell protein nanocapsules containing the 2.4 MDa apoptin complexes. Recombinant apoptin is reversibly encapsulated in a positively charged, water soluble polymer shell and is released in native form in response to reducing conditions such as the cytoplasm. As characterized by confocal microscopy, the nanocapsules are efficiently internalized by mammalian cells lines, with accumulation of rhodamine-labeled apoptin in the nuclei of cancer cells only. Intracellularly released apoptin induced tumor-specific apoptosis in several cancer cell lines and inhibited tumor growth in vivo, demonstrating the potential of this polymer–protein combination as an anticancer therapeutic.}, number={1}, journal={Nano Today}, publisher={Elsevier BV}, author={Zhao, Muxun and Hu, Biliang and Gu, Zhen and Joo, Kye-Il and Wang, Pin and Tang, Yi}, year={2013}, month={Feb}, pages={11–20} }
 @article{zhang_pelet_heller_dong_chen_gu_joseph_wallas_anderson_2013, title={Drug Delivery: Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery (Adv. Mater. 33/2013)}, volume={25}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201370207}, DOI={10.1002/ADMA.201370207}, abstractNote={The self-assembled nanoparticles for siRNA delivery with lipid-modified aminoglycoside derivatives is described by Daniel G. Anderson and co-workers on page 4641. The core-shell nanoparticles can protect siRNA from enzymatic degradation within the body and subsequently deliver siRNA into cytoplasm of target cells. The image is courtesy of Dr. Ning Zhang.}, number={33}, journal={Advanced Materials}, publisher={Wiley}, author={Zhang, Yunlong and Pelet, Jeisa M. and Heller, Daniel A. and Dong, Yizhou and Chen, Delai and Gu, Zhen and Joseph, Brian J. and Wallas, Jasmine and Anderson, Daniel G.}, year={2013}, month={Sep}, pages={4680–4680} }
 @article{dang_thai_cohen_slosberg_siniakowicz_doloff_ma_hollister-lock_tang_gu_et al._2013, title={Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug}, volume={34}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/J.BIOMATERIALS.2013.04.016}, DOI={10.1016/J.BIOMATERIALS.2013.04.016}, abstractNote={Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes.}, number={23}, journal={Biomaterials}, publisher={Elsevier BV}, author={Dang, Tram T. and Thai, Anh V. and Cohen, Joshua and Slosberg, Jeremy E. and Siniakowicz, Karolina and Doloff, Joshua C. and Ma, Minglin and Hollister-Lock, Jennifer and Tang, Katherine M. and Gu, Zhen and et al.}, year={2013}, month={Jul}, pages={5792–5801} }
 @article{gu_dang_ma_tang_cheng_jiang_dong_zhang_anderson_2013, title={Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery}, volume={7}, ISSN={["1936-086X"]}, DOI={10.1021/nn401617u}, abstractNote={A glucose-responsive closed-loop insulin delivery system represents the ideal treatment of type 1 diabetes mellitus. In this study, we develop uniform injectable microgels for controlled glucose-responsive release of insulin. Monodisperse microgels (256 ± 18 μm), consisting of a pH-responsive chitosan matrix, enzyme nanocapsules, and recombinant human insulin, were fabricated through a one-step electrospray procedure. Glucose-specific enzymes were covalently encapsulated into the nanocapsules to improve enzymatic stability by protecting from denaturation and immunogenicity as well as to minimize loss due to diffusion from the matrix. The microgel system swelled when subjected to hyperglycemic conditions, as a result of the enzymatic conversion of glucose into gluconic acid and protonation of the chitosan network. Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. Finally, we demonstrated that these microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes.}, number={8}, journal={ACS NANO}, author={Gu, Zhen and Dang, Tram T. and Ma, Minglin and Tang, Benjamin C. and Cheng, Hao and Jiang, Shan and Dong, Yizhou and Zhang, Yunlong and Anderson, Daniel G.}, year={2013}, month={Aug}, pages={6758–6766} }
 @article{wang_gu_jamal_detamore_berkland_2013, title={Hybrid Hydroxyapatite Nanoparticle Colloidal Gels are Injectable Fillers for Bone Tissue Engineering}, volume={19}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2013.0075}, abstractNote={Injectable bone fillers have emerged as an alternative to the invasive surgery often required to treat bone defects. Current bone fillers may benefit from improvements in dynamic properties such as shear thinning during injection and recovery of material stiffness after placement. Negatively charged inorganic hydroxyapatite (HAp) nanoparticles (NPs) were assembled with positively charged organic poly(d,l-lactic-co-glycolic acid) (PLGA) NPs to create a cohesive colloidal gel. This material is held together by electrostatic forces that may be disrupted by shear to facilitate extrusion, molding, or injection. Scanning electron micrographs of the dried colloidal gels showed a well-organized, three-dimensional porous structure. Rheology tests revealed that certain colloidal gels could recover after being sheared. Human umbilical cord mesenchymal stem cells were also highly viable when seeded on the colloidal gels. HAp/PLGA NP colloidal gels offer an attractive scheme for injectable filling and regeneration of bone tissue.}, number={23-24}, journal={TISSUE ENGINEERING PART A}, author={Wang, Qun and Gu, Zhen and Jamal, Syed and Detamore, Michael S. and Berkland, Cory}, year={2013}, month={Dec}, pages={2586–2593} }
 @article{gu_aimetti_wang_dang_zhang_veiseh_cheng_langer_anderson_2013, title={Injectable Nano-Network for Glucose-Mediated Insulin Delivery}, volume={7}, ISSN={["1936-086X"]}, DOI={10.1021/nn400630x}, abstractNote={Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.}, number={5}, journal={ACS NANO}, author={Gu, Zhen and Aimetti, Alex A. and Wang, Qun and Dang, Tram T. and Zhang, Yunlong and Veiseh, Omid and Cheng, Hao and Langer, Robert S. and Anderson, Daniel G.}, year={2013}, month={May}, pages={4194–4201} }
 @article{zhang_pelet_heller_dong_chen_gu_joseph_wallas_anderson_2013, title={Lipid-Modified Aminoglycoside Derivatives for In Vivo siRNA Delivery}, volume={25}, ISSN={0935-9648}, url={http://dx.doi.org/10.1002/ADMA.201301917}, DOI={10.1002/ADMA.201301917}, abstractNote={Rationally designed siRNA delivery materials that are enabled by lipid-modified aminoglycosides are demonstrated. Leading materials identified are able to self-assemble with siRNA into well-defined nanoparticles and induce efficient gene knockdown both in vitro and in vivo. Histology studies and liver function tests reveal that no apparent toxicity is caused by these nanoparticles at doses over two orders of magnitude.}, number={33}, journal={Advanced Materials}, publisher={Wiley}, author={Zhang, Yunlong and Pelet, Jeisa M. and Heller, Daniel A. and Dong, Yizhou and Chen, Delai and Gu, Zhen and Joseph, Brian J. and Wallas, Jasmine and Anderson, Daniel G.}, year={2013}, month={Jun}, pages={4641–4645} }
 @article{di_price_gu_jiang_jing_gu_2013, title={Ultrasound-Triggered Regulation of Blood Glucose Levels Using Injectable Nano-Network}, volume={3}, ISSN={2192-2640}, url={http://dx.doi.org/10.1002/ADHM.201300490}, DOI={10.1002/adhm.201300490}, abstractNote={The integration of an injectable insulin-encapsulated nano-network with a focused ultrasound system (FUS) can remotely regulate insulin release both in vitro and in vivo. A single subcutaneous injection of the nano-network with intermittent FUS administration facilitates reduction of the blood glucose levels in type 1 diabetic mice for up to 10 d.}, number={6}, journal={Advanced Healthcare Materials}, publisher={Wiley}, author={Di, Jin and Price, Jennifer and Gu, Xiao and Jiang, Xiaoning and Jing, Yun and Gu, Zhen}, year={2013}, month={Nov}, pages={811–816} }
 @article{gu_zhao_sheng_bentolila_tang_2011, title={Detection of Mercury Ion by Infrared Fluorescent Protein and Its Hydrogel-Based Paper Assay}, volume={83}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ac103236g}, DOI={10.1021/ac103236g}, abstractNote={Mercury is a highly hazardous and widespread pollutant with bioaccumulative properties. Novel approaches that meet the criteria of desired selectivity, high sensitivity, good biocompatibility, and low background interference in natural settings are continuously being explored. We herein describe a new strategy utilizing the combination of infrared fluorescent protein (IFP) and its chromophore as an infrared fluorescence probe for mercury ion (Hg(II)) detection. Hg(II) has been validated to have specific binding affinity to a cysteine residue (C24) of IFP, thereby inhibiting the conjugation of IFP chromophore biliverdin (BV) to C24 and "turning off" the infrared emission of IFP. The IFP/BV sensor has high selectivity toward Hg(II) among other metal ions over a broad pH range. The in vitro detection limit was determined to be less than 50 nM. As a genetically encoded probe, we demonstrate the IFP/BV sensor can serve as a tool to detect Hg(II) in living organisms or tissues. Moreover, we have exploited a protein-agarose hydrogel-based paper assay to immobilize IFP for detection of Hg(II) in a portable and robust fashion.}, number={6}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Gu, Zhen and Zhao, Muxun and Sheng, Yuewei and Bentolila, Laurent A. and Tang, Yi}, year={2011}, month={Mar}, pages={2324–2329} }
 @article{biswas_joo_liu_zhao_fan_wang_gu_tang_2011, title={Endoprotease-Mediated Intracellular Protein Delivery Using Nanocapsules}, volume={5}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/nn1031005}, DOI={10.1021/nn1031005}, abstractNote={Proteins possess distinct intracellular roles allowing them to have vast therapeutic applications. However, due to poor cellular permeability and fragility of most proteins, intracellular delivery of native, active proteins is challenging. We describe a biomimetic protein delivery vehicle which is degradable upon the digestion by furin, a ubiquitous intracellular protease, to release encapsulated cargos. Proteins were encapsulated in a nanosized matrix prepared with monomers and a bisacrylated peptide cross-linker which can be specifically recognized and cleaved by furin. Release of encapsulated protein was confirmed in a cell-free system upon proteolytic degradation of nanocapsules. In vitro cell culture studies demonstrated successful intracellular delivery of both nuclear and cytosolic proteins and confirmed the importance of furin-degradable construction for native protein release. This endoprotease-mediated intracellular delivery system may be extended to effectively deliver various biological therapeutics.}, number={2}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Biswas, Anuradha and Joo, Kye-Il and Liu, Jing and Zhao, Muxun and Fan, Guoping and Wang, Pin and Gu, Zhen and Tang, Yi}, year={2011}, month={Jan}, pages={1385–1394} }
 @article{joo_fang_liu_xiao_gu_tai_lee_tang_wang_2011, title={Enhanced Real-Time Monitoring of Adeno-Associated Virus Trafficking by Virus–Quantum Dot Conjugates}, volume={5}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/nn102651p}, DOI={10.1021/nn102651p}, abstractNote={The unique spectral properties of semiconductor quantum dots (QDs) enable long-term live-cell imaging and ultrasensitive detection of viral particles, which in turn can potentially provide a practical means for detailed analysis of the underlying molecular mechanisms of virus entry. In this study, we report a general method of labeling adeno-associated virus serotype 2 (AAV2) with QDs for enhanced visualization of the intracellular behavior of viruses in living target cells. It was found that the mild conditions required for this QD conjugation reaction allowed for the retention of viral infectivity of AAV2. Furthermore, quantitative analysis of viral motility in living cells suggested that QD-labeling had no significant effect on the intracellular transport properties of AAV2 particles compared to those of conventional organic dye-labeled AAV2. Our imaging study demonstrated that QD-AAV2 was internalized mainly through a clathrin-dependent pathway and then trafficked through various endosomes. It was also observed that QD-AAV2 particles exploit the cytoskeleton network to facilitate their transport within cells, and the labeling study provided evidence that the ubiquitin-proteasome system was likely involved in the intracellular trafficking of AAV2, at least at the level of nuclear transport. Taken together, our findings reveal the potential of this QD-labeling method for monitoring the intracellular dynamics of virus-host cell interactions and interrogating the molecular mechanisms of viral infection in greater detail.}, number={5}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Joo, Kye-Il and Fang, Yun and Liu, Yarong and Xiao, Liang and Gu, Zhen and Tai, April and Lee, Chi-Lin and Tang, Yi and Wang, Pin}, year={2011}, month={Apr}, pages={3523–3535} }
 @article{zhao_biswas_hu_joo_wang_gu_tang_2011, title={Redox-responsive nanocapsules for intracellular protein delivery}, volume={32}, ISSN={0142-9612}, url={http://dx.doi.org/10.1016/j.biomaterials.2011.03.060}, DOI={10.1016/j.biomaterials.2011.03.060}, abstractNote={Direct delivery of proteins to the cytosol of cells holds tremendous potential in biological and medical applications. Engineering vehicles for escorting proteins to the cytosol in a controlled release fashion has thus generated considerable interest. We report here the preparation of redox-responsive single-protein nanocapsules for intracellular protein delivery. Through in situ interfacial polymerization, the target protein is noncovalently encapsulated into a positively-charged polymeric shell interconnected by disulfide-containing crosslinkers. The dissociation of the polymeric shell under reducing conditions and the subsequent release of protein were confirmed using cell-free assays in the presence of glutathione (GSH). The nanocapsules were demonstrated to be efficiently internalized into the cells and to release the protein in the reducing cytosol. Using the nanocapsule as a vehicle, we showed that active caspase 3 (CP-3) can be delivered and can induce apoptosis in a variety of human cancer cell lines, including HeLa, MCF-7 and U-87 MG. Our approach therefore presents an effective intracellular protein delivery strategy for therapeutic, diagnostic and reprogramming applications.}, number={22}, journal={Biomaterials}, publisher={Elsevier BV}, author={Zhao, Muxun and Biswas, Anuradha and Hu, Biliang and Joo, Kye-Il and Wang, Pin and Gu, Zhen and Tang, Yi}, year={2011}, month={Aug}, pages={5223–5230} }
 @article{gu_biswas_zhao_tang_2011, title={Tailoring nanocarriers for intracellular protein delivery}, volume={40}, ISSN={0306-0012 1460-4744}, url={http://dx.doi.org/10.1039/c0cs00227e}, DOI={10.1039/c0cs00227e}, abstractNote={Proteins play a crucial role in life, taking part in all vital processes in the body. In the past decade, there was increasing interest in delivering active forms of proteins to specific cells and organs. Intracellular protein delivery holds enormous promise for biological and medical applications, including cancer therapy, vaccination, regenerative medicine, treatment for loss-of-function genetic diseases and imaging. This tutorial review surveys recent developments in intracellular protein delivery using various nanocarriers. Methods such as lipid-mediated colloidal systems, polymeric nanocarriers, inorganic systems and protein-mediated carriers are reviewed. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.}, number={7}, journal={Chemical Society Reviews}, publisher={Royal Society of Chemistry (RSC)}, author={Gu, Zhen and Biswas, Anuradha and Zhao, Muxun and Tang, Yi}, year={2011}, pages={3638} }
 @article{sun_sun_gu_shen_jiang_xu_wang_2010, title={Conjugated Polymer Fluorescence Probe for Intracellular Imaging of Magnetic Nanoparticles}, volume={43}, ISSN={0024-9297 1520-5835}, url={http://dx.doi.org/10.1021/ma101680g}, DOI={10.1021/ma101680g}, abstractNote={Bifunctional composite nanoparticles with simultaneous response toward light excitation and external magnetic field are fabricated by electrostatic adsorption of a single layer of conjugated polyelectrolytes on the magnetic nanoparticle surfaces. Cell imaging is realized through incubation of the composite nanoparticles with human hepatoma cell Bel-7402. Both fluorescence microscopy imaging and flow cytometry analysis verify that the bifunctional nanoparticles efficiently penetrate the cell membranes. Transmission electron microscopy reveals that the nanoparticles are confined in the endosome and show clear signs of particle aggregation. The cellular uptake efficiencies of the magnetic-fluorescent nanoparticles can be enhanced greatly by a magnetic field. In vitro cell viability results indicate low cytotoxicity of the nanoparticles even after 72 h incubation. The current method of fluorescence labeling of nanomaterials by electrostatic adsorption is applicable to a variety of charged nanomaterials that e...}, number={24}, journal={Macromolecules}, publisher={American Chemical Society (ACS)}, author={Sun, Bin and Sun, Min-Jie and Gu, Zhen and Shen, Qun-Dong and Jiang, Shao-Jun and Xu, Ying and Wang, Yu}, year={2010}, month={Dec}, pages={10348–10354} }
 @article{gu_tang_2010, title={Enzyme-assisted photolithography for spatial functionalization of hydrogels}, volume={10}, ISSN={1473-0197 1473-0189}, url={http://dx.doi.org/10.1039/c001335h}, DOI={10.1039/c001335h}, abstractNote={The ability to form functional polymeric patterning structures has important implications for the studies of cell biology, tissue engineering, and medical diagnostics. We have developed a novel enzyme-assisted photolithography (EAPL) method for spatial functionalization of hydrogels via a high throughput fashion. A bisacrylated peptide crosslinker, containing a protease cleavable amino acid sequence and caged by a photolabile moiety, is used during hydrogel polymerization. A facile two-step process is employed, including UV exposure to decage the peptide crosslinker at a desired area and protease development to specifically digest gels at UV treated regions only. Importantly, proteolysis of the peptide bonds generates free nucleophilic amine groups at the patterned area that can be further functionalized. Using this strategy and caspase-3 as the enzyme developer, we demonstrate the simultaneous generation of topographical and functional patterns into poly(ethylene glycol) (PEG) hydrogels. We show that 20 microm-wide line arrays functionalized with arginine-glycine-aspartic acid (RGD)-containing peptides can be used to generate cell patterns with individual cell resolution. We also fabricated arrays 20 mum diameter cavities decorated with B lymphocyte specific anti-CD19, which was used to achieve a 600-fold enrichment of B-cells from a 0.1% starting B-cell mixture. The simple fabrication process, straightforward chemistry and an all-aqueous based biocompatible and environmentally friendly approach render EAPL a versatile platform to construct biologically responsive 2D patterns or 3D scaffolds for lab-on-a-chip systems and tissue engineering.}, number={15}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Gu, Zhen and Tang, Yi}, year={2010}, pages={1946} }
 @article{gu_chen_shen_ge_xu_2010, title={Hybrid nanocomposites of semiconductor nanoparticles and conjugated polyelectrolytes and their application as fluorescence biosensors}, volume={51}, ISSN={0032-3861}, url={http://dx.doi.org/10.1016/j.polymer.2009.12.035}, DOI={10.1016/j.polymer.2009.12.035}, abstractNote={Weakly emissive silicon nanoparticles with an average diameter of about 5 nm are prepared via pulsed laser ablation of silicon wafers in water. Electrostatic assembly of water-soluble conjugated polyelectrolytes on the surface of the silicon nanoparticles steadily enhances the photoluminescence of these nanocomposites, indicating the possibility of energy transfer between the semiconductor nanoparticles and the conjugated polymer, or silicon nanoparticle-induced elimination of chain aggregates of the conjugated polyelectrolyte. Fluorescence emission of the hybrid silicon-conjugated polymer nanocomposites is steeply quenched by cytochrome c, and the minimum detection concentration for the redox-active protein is found to be 50 nM. The sensitization is realized by ultrafast photoinduced electron transfer between the electron-deficient protein and the conjugated polyelectrolyte binding on the silicon nanoparticle surfaces. The results offer guidelines to explore novel sensors for detecting nanoparticles, and also help develop high-efficiency sensory materials based on electrostatic complexes of conjugated polyelectrolytes and inorganic semiconductor nanoparticles.}, number={4}, journal={Polymer}, publisher={Elsevier BV}, author={Gu, Zhen and Chen, Xiao-Yuan and Shen, Qun-Dong and Ge, Hai-Xiong and Xu, Hai-Hua}, year={2010}, month={Feb}, pages={902–907} }
 @article{gu_biswas_joo_hu_wang_tang_2010, title={Probing protease activity by single-fluorescent-protein nanocapsules}, volume={46}, ISSN={1359-7345 1364-548X}, url={http://dx.doi.org/10.1039/c0cc01439g}, DOI={10.1039/c0cc01439g}, abstractNote={We describe a FRET-based protease detection strategy, using a single-fluorescent-protein nanogel as donor and a dark quencher as acceptor linked by a photolabile caged-peptide. This design enables probing of protease activity in a UV-responsive fashion.}, number={35}, journal={Chemical Communications}, publisher={Royal Society of Chemistry (RSC)}, author={Gu, Zhen and Biswas, Anuradha and Joo, Kye-Il and Hu, Biliang and Wang, Pin and Tang, Yi}, year={2010}, pages={6467} }
 @article{yan_du_gu_liang_hu_zhang_priceman_wu_zhou_liu_et al._2009, title={A novel intracellular protein delivery platform based on single-protein nanocapsules}, volume={5}, ISSN={1748-3387 1748-3395}, url={http://dx.doi.org/10.1038/nnano.2009.341}, DOI={10.1038/nnano.2009.341}, abstractNote={An average cell contains thousands of proteins that participate in normal cellular functions, and most diseases are somehow related to the malfunctioning of one or more of these proteins. Protein therapy, which delivers proteins into the cell to replace the dysfunctional protein, is considered the most direct and safe approach for treating disease. However, the effectiveness of this method has been limited by its low delivery efficiency and poor stability against proteases in the cell, which digest the protein. Here, we show a novel delivery platform based on nanocapsules consisting of a protein core and a thin permeable polymeric shell that can be engineered to either degrade or remain stable at different pHs. Non-degradable capsules show long-term stability, whereas the degradable ones break down their shells, enabling the core protein to be active once inside the cells. Multiple proteins can be delivered to cells with high efficiency while maintaining low toxicity, suggesting potential applications in imaging, therapy and cosmetics fields.}, number={1}, journal={Nature Nanotechnology}, publisher={Springer Science and Business Media LLC}, author={Yan, Ming and Du, Juanjuan and Gu, Zhen and Liang, Min and Hu, Yufang and Zhang, Wenjun and Priceman, Saul and Wu, Lily and Zhou, Z. Hong and Liu, Zheng and et al.}, year={2009}, month={Nov}, pages={48–53} }
 @article{gu_huang_chen_2009, title={Biomolecular Nanopatterning by Magnetic Electric Lithography}, volume={48}, ISSN={1433-7851 1521-3773}, url={http://dx.doi.org/10.1002/anie.200803456}, DOI={10.1002/anie.200803456}, abstractNote={Paint by number? Magnetic nanoparticles (MNPs) coated with distinct biomolecules (see picture) can be assembled onto nanoelectrodes on a template under the control of magnetic and electric fields. The MNP-biomolecule conjugates can then be transferred from the template to a biocompatible polymer substrate. Arbitrary nanopatterns can be fabricated by the magnetic electric lithography process over a large area with a resolution down to 10 nm.}, number={5}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Gu, Zhen and Huang, Suxian and Chen, Yong}, year={2009}, month={Jan}, pages={952–955} }
 @article{gu_huang_chen_2009, title={Cover Picture: Biomolecular Nanopatterning by Magnetic Electric Lithography (Angew. Chem. Int. Ed. 5/2009)}, volume={48}, ISSN={1433-7851 1521-3773}, url={http://dx.doi.org/10.1002/anie.200990006}, DOI={10.1002/anie.200990006}, abstractNote={Biomolecular nanopatterns can be quickly fabricated over a large area with a resolution down to 10 nm by magnetic electric lithography, as reported by Z. Gu, S. Huang, and Y. Chen in their Communication on page 952 ff. Magnetic nanoparticles coated with multiple distinct biomolecules are deposited by a magnetic field and immobilized onto nanoelectrodes by an electric field to generate arbitrary heterogeneous biomolecular nanopatterns, which can then be printed onto polymer films for diverse biomedical applications.}, number={5}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Gu, Zhen and Huang, Suxian and Chen, Yong}, year={2009}, month={Jan}, pages={829–829} }
 @article{gu_yan_hu_joo_biswas_huang_lu_wang_tang_2009, title={Protein Nanocapsule Weaved with Enzymatically Degradable Polymeric Network}, volume={9}, ISSN={1530-6984 1530-6992}, url={http://dx.doi.org/10.1021/nl902935b}, DOI={10.1021/nl902935b}, abstractNote={Target proteins can be functionally encapsulated using a cocoon-like polymeric nanocapsule formed by interfacial polymerization. The nanocapsule is cross-linked by peptides that can be proteolyzed by proteases upon which the protein cargo is released. The protease-mediated degradation process can be controlled in a spatiotemporal fashion through modification of the peptide cross-linker with photolabile moieties. We demonstrate the utility of this approach through the cytoplasmic delivery of the apoptosis inducing caspase-3 to cancer cells.}, number={12}, journal={Nano Letters}, publisher={American Chemical Society (ACS)}, author={Gu, Zhen and Yan, Ming and Hu, Biliang and Joo, Kye-Il and Biswas, Anuradha and Huang, Yu and Lu, Yunfeng and Wang, Pin and Tang, Yi}, year={2009}, month={Dec}, pages={4533–4538} }
 @article{lai_li_zhang_li_stickle_zhu_gu_kamins_williams_chen_2008, title={An Organic/Si Nanowire Hybrid Field Configurable Transistor}, volume={8}, ISSN={1530-6984 1530-6992}, url={http://dx.doi.org/10.1021/nl073112y}, DOI={10.1021/nl073112y}, abstractNote={We report a field configurable transistor (FCT) fabricated on a Si nanowire FET platform by integrating a thin film of conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV) and an ionic conductive layer (RbAg4I5) into the gate. The FCT can be precisely configured to desired nonvolatile analog state dynamically, repeatedly, and reversibly by controlling the concentration of iodide ions in the MEH-PPV layer with a gate voltage. The flexible configurability and plasticity of the FCT could facilitate field-programmable circuits for defect-tolerance and synapse-like devices for learning.}, number={3}, journal={Nano Letters}, publisher={American Chemical Society (ACS)}, author={Lai, Qianxi and Li, Zhiyong and Zhang, Lei and Li, Xuema and Stickle, William F. and Zhu, Zuhua and Gu, Zhen and Kamins, Theodore I. and Williams, R. Stanley and Chen, Yong}, year={2008}, month={Mar}, pages={876–880} }
 @article{gu_bao_zhang_wang_shen_2006, title={Anionic Water-Soluble Poly(phenylenevinylene) Alternating Copolymer:  High-Efficiency Photoluminescence and Dual Electroluminescence}, volume={39}, ISSN={0024-9297 1520-5835}, url={http://dx.doi.org/10.1021/ma052741w}, DOI={10.1021/ma052741w}, abstractNote={A facile chemical approach to enhance the photoluminescence of poly(2-methoxy-5-propyloxysulfonate-1,4-phenylenevinylene) (MPS-PPV) by alternately incorporating the rigid p-phenylenevinylene comonomer units into the conjugated backbone is reported. In dilute aqueous solution the resulting anionic conjugated copolymer, poly[(2-methoxy-5-propyloxysulfonate-1,4-phenylenevinylene)-alt-(1,4-phenylenevinylene)] (CO-MPS-PPV), has a fluorescence quantum yield of 51.6%, about an order of magnitude higher than that of the homopolymer. Because of their amphiphilic nature, CO-MPS-PPV chains self-organize into micelle-like aggregates in water. The structure changes of the aggregates can be perceived through monitoring photoluminescence spectra at different solvent compositions and pH values. The fluorescence of the conjugated copolymer solution is highly sensitive to the cationic surfactant, and emission can be drastically quenched to about 5% of original intensity in the presence of extremely low concentration (26 μm...}, number={9}, journal={Macromolecules}, publisher={American Chemical Society (ACS)}, author={Gu, Zhen and Bao, Yong-Jun and Zhang, Yang and Wang, Mu and Shen, Qun-Dong}, year={2006}, month={May}, pages={3125–3131} }
 @article{gu_shen_zhang_yang_bao_2006, title={Dual electroluminescence from a single-component light-emitting electrochemical cell, based on water-soluble conjugated polymer}, volume={100}, ISSN={0021-8995 1097-4628}, url={http://dx.doi.org/10.1002/app.22510}, DOI={10.1002/app.22510}, abstractNote={Abstract}, number={4}, journal={Journal of Applied Polymer Science}, publisher={Wiley}, author={Gu, Zhen and Shen, Qun-Dong and Zhang, Juan and Yang, Chang-Zheng and Bao, Yong-Jun}, year={2006}, pages={2930–2936} }
 @article{wang_ye_yu_kahkoska_zhang_wang_sun_corder_chen_khan_et al., title={Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery}, volume={12}, number={3}, journal={ACS Nano}, author={Wang, J. Q. and Ye, Y. Q. and Yu, J. C. and Kahkoska, A. R. and Zhang, X. D. and Wang, C. and Sun, W. J. and Corder, R. D. and Chen, Z. W. and Khan, S. A. and et al.}, pages={2466–2473} }
 @article{jiang_sun_zhu_burns_khan_mo_gu, title={Furin-mediated sequential delivery of anticancer cytokine and small-molecule drug shuttled by graphene}, volume={27}, number={6}, journal={Advanced Materials}, author={Jiang, T. Y. and Sun, W. J. and Zhu, Q. W. and Burns, N. A. and Khan, S. A. and Mo, R. and Gu, Z.}, pages={1021–1028} }