@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{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{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{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{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{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{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{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{liu_tsai_zeng_cheng_jiang_chen_zhang_zhang_mei_2018, title={Phosphorylcholine-based stealthy nanocapsules decorating TPGS for combatting multi-drug-resistant cancer}, volume={4}, number={5}, journal={ACS Biomaterials-Science & Engineering}, author={Liu, G. and Tsai, H. I. and Zeng, X. W. and Cheng, W. and Jiang, L. J. and Chen, H. B. and Zhang, X. D. and Zhang, J. X. and Mei, L.}, year={2018}, pages={1679–1686} } @article{jiang_liang_liu_zhou_ye_chen_miao_gao_zhang_mei_2018, title={The mechanism of lauric acid-modified protein nanocapsules escape from intercellular trafficking vesicles and its implication for drug delivery}, volume={25}, number={1}, journal={Drug Delivery}, author={Jiang, L. J. and Liang, X. and Liu, G. and Zhou, Y. and Ye, X. Y. and Chen, X. L. and Miao, Q. W. and Gao, L. and Zhang, X. D. and Mei, L.}, year={2018}, pages={985–994} } @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{zhang_hao_xu_gao_wang_zhu_chen_zhang_chen_mei_2017, title={A pH-sensitive methenamine mandelate-loaded nanoparticle induces DNA damage and apoptosis of cancer cells}, volume={62}, journal={Acta Biomaterialia}, author={Zhang, L. H. and Hao, W. B. and Xu, L. and Gao, Y. F. and Wang, X. S. and Zhu, D. W. and Chen, Z. and Zhang, X. D. and Chen, H. B. and Mei, L.}, year={2017}, pages={246–256} } @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{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{zhang_chang_yang_zhang_tao_jiang_liang_tsai_huang_mei_2017, title={Systematic investigation on the intracellular trafficking network of polymeric nanoparticles}, volume={9}, number={9}, journal={Nanoscale}, author={Zhang, J. X. and Chang, D. F. and Yang, Y. and Zhang, X. D. and Tao, W. and Jiang, L. J. and Liang, X. and Tsai, H. G. and Huang, L. Q. and Mei, L.}, year={2017}, pages={3269–3282} } @article{zhang_zhang_liang_zhang_tao_zhu_chang_zeng_mei_2016, title={Iron oxide nanoparticles induce autophagosome accumulation through multiple mechanisms: Lysosome impairment, mitochondrial damage, and ER stress}, volume={13}, number={7}, journal={Molecular Pharmaceutics}, author={Zhang, X. D. and Zhang, H. Q. and Liang, X. and Zhang, J. X. and Tao, W. and Zhu, X. B. and Chang, D. F. and Zeng, X. W. and Mei, L.}, year={2016}, pages={2578–2587} } @article{zhang_zhang_liu_chang_liang_zhu_tao_mei_2016, title={intracellular trafficking network of protein nanocapsules: endocytosis, exocytosis and autophagy}, volume={6}, number={12}, journal={Theranostics}, author={Zhang, J. X. and Zhang, X. D. and Liu, G. and Chang, D. F. and Liang, X. and Zhu, X. B. and Tao, W. and Mei, L.}, year={2016}, pages={2099–2113} } @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} }