@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{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} } @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={

Summary

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} } @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{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} } @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{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{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} } @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{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{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{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{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{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{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_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} } @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{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{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{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{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} }