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