@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. A hydrogel implanted into the cavity of a resected tumour and releasing CAR-T cells and platelets conjugated with a checkpoint inhibitor inhibits local tumour recurrence and the growth of distant tumours in mice.}, 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{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{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={<h2>Summary</h2> 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<sup>+</sup> and CD8<sup>+</sup> 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_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-+} }
 @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} }
 @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{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} }
 @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_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{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} }