@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{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{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} } @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{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{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} } @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{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{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} }