@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{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.}, 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{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{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={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_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} } @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{hu_chen_gu_2018, title={Advances in transformable drug delivery systems}, volume={178}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2018.03.056}, abstractNote={These years, transformable drug delivery systems (DDSs), which hold the capability of changing formulation morphology and subsequent functionality at the desired disease site, have shown great promise in control of spatio-temporal drug delivery/release manner and enhanced treatment efficacy. Equipped with controllability and design flexibility, the transformable DDSs are being increasingly pursued for the development of precision drug delivery platforms for biomedical applications. In this review, we describe the recently developed intracelluarly and extracellularly transformable DDSs, especially associated with assembly or disassociation of the original formulation units, for achieving various functionalities, including prolonged retention time, inhibited endocytosis and enhanced cytotoxicity. Furthermore, the different stimuli, such as pH, enzyme, light, temperature, redox and mechanical force that trigger the transformation process are also introduced. The future outlook and challenges are discussed in the end.}, journal={BIOMATERIALS}, author={Hu, Quanyin and Chen, Qian and Gu, Zhen}, year={2018}, month={Sep}, pages={546–558} } @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{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_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} } @misc{chen_hu_gu_2018, title={Leveraging Engineering of Cells for Drug Delivery}, volume={51}, ISSN={["1520-4898"]}, DOI={10.1021/acs.accounts.7b00526}, abstractNote={Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns. As a recent emerging research topic, drawing inspiration from the ways that natural cells interact with the body has opened new avenues for cell engineering, such as direct modification of whole cells with synthetic materials and "top-down" integration of biological membranes with micro/nanomaterials, which aim to alleviate immune response while harnessing the complex biological functions of cells. In this Account, we summarize our recent contribution to the field of cell engineering methodologies, with which we have demonstrated their promising applications for cancer immunotherapy, targeted drug delivery, and blood glucose regulation. For example, inspired by the inherent ability of platelets to accumulate at wound sites and interact with circulating tumor cells, we exploited a targeted checkpoint antibody delivery strategy for treatment of postsurgical cancer recurrence and metastatic spread by covalent binding of platelets' cell surfaces with a monoclonal antibody against programmed-death ligand 1 (aPDL1). Without interfering with the platelets' surgical-site homing property, the conjugated aPDL1 could be triggered to release in the form of microparticles after in situ activation. As an extension, we then engineered the platelet membrane to cloak nanoparticles for anticancer drug delivery, mimicking the targeting capability of the source cells while possessing prolonged circulation lifetime and insignificant immunogenicity. At the same time, we also found that the subcellular compartment membrane-derived particulates exhibited high specificity toward homotypic cells, by which enhanced intracellular drug delivery was achieved. Moreover, by taking advantage of the reversible interaction between glucose-derivative-modified insulin and the red blood cell membrane, we constructed a glucose-responsive smart insulin delivery system for long-term maintenance of blood glucose levels within a normal range. Recently, by virtue of painless microneedle patches as convenient cell engineering platforms, a minimally invasive intradermal antitumor vaccine was invented by integrating whole-tumor lysis into near-infrared light-illuminated microneedle patches. The microneedle patches also showed promise in combining with conventional cell encapsulation techniques, by which an externally positioned β-cell engineering strategy was proposed for diabetes treatment. The results presented in this Account demonstrate distinct approaches to the development and application of cell engineering strategies for drug delivery.}, number={3}, journal={ACCOUNTS OF CHEMICAL RESEARCH}, author={Chen, Zhaowei and Hu, Quanyin and Gu, Zhen}, year={2018}, month={Mar}, pages={668–677} } @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{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{qian_feng_yu_chen_hu_sun_xiao_hu_bellotti_shen_et al._2017, title={Anaerobe-Inspired Anticancer Nanovesicles}, volume={56}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201611783}, abstractNote={Abstract}, number={10}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Qian, Chenggen and Feng, Peijian and Yu, Jicheng and Chen, Yulei and Hu, Quanyin and Sun, Wujin and Xiao, Xuanzhong and Hu, Xiuli and Bellotti, Adriano and Shen, Qun-Dong and et al.}, year={2017}, month={Mar}, pages={2588–2593} } @misc{cheng-gen_chen_feng_xiao_dong_yu_hu_shen_gu_2017, title={Conjugated polymer nanomaterials for theranostics}, volume={38}, ISSN={["1745-7254"]}, DOI={10.1038/aps.2017.42}, abstractNote={Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrared (NIR) imaging, two-photon (TP) imaging, photoacoustic (PA) imaging, and multimodal (MM) imaging, are introduced. Then, CPN-based photodynamic therapy (PDT) and photothermal therapy (PTT) are surveyed. A variety of stimuli-responsive CPN systems for drug delivery are also summarized, and the promising trends and translational challenges are discussed.}, number={6}, journal={ACTA PHARMACOLOGICA SINICA}, author={Cheng-gen, Qian and Chen, Yu-lei and Feng, Pei-jian and Xiao, Xuan-zhong and Dong, Mei and Yu, Ji-cheng and Hu, Quan-yin and Shen, Qun-dong and Gu, Zhen}, year={2017}, month={Jun}, pages={764–781} } @misc{hu_bomba_gu_2017, title={Engineering platelet-mimicking drug delivery vehicles}, volume={11}, ISSN={["2095-0187"]}, DOI={10.1007/s11705-017-1614-6}, number={4}, journal={FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING}, author={Hu, Quanyin and Bomba, Hunter N. and Gu, Zhen}, year={2017}, month={Dec}, pages={624–632} } @article{lu_lin_chen_hu_liu_yu_gao_dickey_gu_2017, title={Enhanced Endosomal Escape by Light-Fueled Liquid-Metal Transformer}, volume={17}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.6b04346}, abstractNote={Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal. When coated with graphene quantum dots (GQDs), the resulting nanospheres demonstrate the ability to absorb and convert photoenergy to drive the simultaneous phase separation and morphological transformation of the inner liquid-metal core. The morphological transformation from nanospheres to hollow nanorods with a remarkable change of aspect ratio can physically disrupt the endosomal membrane to promote endosomal escape of payloads. This metal-based nanotransformer equipped with GQDs provides a new strategy for facilitating effective endosomal escape to achieve spatiotemporally controlled drug delivery with enhanced efficacy.}, number={4}, journal={NANO LETTERS}, publisher={American Chemical Society (ACS)}, author={Lu, Yue and Lin, Yiliang and Chen, Zhaowei and Hu, Quanyin and Liu, Yang and Yu, Shuangjiang and Gao, Wei and Dickey, Michael D. and Gu, Zhen}, year={2017}, month={Apr}, pages={2138–2145} } @article{hu_sun_qian_bomba_xin_gu_2017, title={Relay Drug Delivery for Amplifying Targeting Signal and Enhancing Anticancer Efficacy}, volume={29}, ISSN={["1521-4095"]}, DOI={10.1002/adma.201605803}, abstractNote={A "relay drug delivery" system based on two distinct modules, which is composed of a signal transmission nanocarrier A (NCA ) that can specifically induce tumor blood vessel inflammation generation and an execution biomimetic nanocarrier B (NCB ) that can accumulate at the tumor site by receiving the broadcasting signals generated by NCA , is developed for amplifying active tumor targeting signal and enhancing antitumor therapy.}, number={13}, journal={ADVANCED MATERIALS}, author={Hu, Quanyin and Sun, Wujin and Qian, Chenggen and Bomba, Hunter N. and Xin, Hongliang and Gu, Zhen}, year={2017}, month={Apr} } @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{qian_chen_zhu_yu_zhang_feng_tang_hu_sun_lu_et al._2016, title={ATP-Responsive and Near-Infrared-Emissive Nanocarriers for Anticancer Drug Delivery and Real-Time Imaging}, volume={6}, ISSN={["1838-7640"]}, DOI={10.7150/thno.14843}, abstractNote={Stimuli-responsive and imaging-guided drug delivery systems hold vast promise for enhancement of therapeutic efficacy. Here we report an adenosine-5'-triphosphate (ATP)-responsive and near-infrared (NIR)-emissive conjugated polymer-based nanocarrier for the controlled release of anticancer drugs and real-time imaging. We demonstrate that the conjugated polymeric nanocarriers functionalized with phenylboronic acid tags on surface as binding sites for ATP could be converted to the water-soluble conjugated polyelectrolytes in an ATP-rich environment, which promotes the disassembly of the drug carrier and subsequent release of the cargo. In vivo studies validate that this formulation exhibits promising capability for inhibition of tumor growth. We also evaluate the metabolism process by monitoring the fluorescence signal of the conjugated polymer through the in vivo NIR imaging.}, number={7}, journal={THERANOSTICS}, author={Qian, Chenggen and Chen, Yulei and Zhu, Sha and Yu, Jicheng and Zhang, Lei and Feng, Peijian and Tang, Xin and Hu, Quanyin and Sun, Wujin and Lu, Yue and et al.}, year={2016}, pages={1053–1064} } @inproceedings{hu_gu_2016, title={Cell membrane-mediated anticancer drug delivery}, volume={1224}, booktitle={Nanotechnology: delivering on the promise, vol 2}, author={Hu, Q. Y. and Gu, Z.}, year={2016}, pages={197–211} } @article{zhao_jiang_lv_wang_lv_wang_liu_liu_hu_sun_et al._2016, title={Dual targeted nanocarrier for brain ischemic stroke treatment}, volume={233}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2016.04.038}, abstractNote={Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Zhao, Yue and Jiang, Yan and Lv, Wei and Wang, Zhongyuan and Lv, Lingyan and Wang, Baoyan and Liu, Xin and Liu, Yang and Hu, Quanyin and Sun, Wujin and et al.}, year={2016}, month={Jul}, pages={64–71} } @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{lv_jiang_liu_wang_lv_zhao_shi_hu_xin_xu_et al._2016, title={Enhanced Antiglioblastoma Efficacy of Neovasculature and Glioma Cells Dual Targeted Nanoparticles}, volume={13}, ISSN={["1543-8384"]}, DOI={10.1021/acs.molpharmaceut.6b00523}, abstractNote={Combining treatment of anticancer cells and antiangiogenesis is considered to be a potential targeted strategy for brain glioblastoma therapy. In this study, by utilizing the overexpression of Interleukin 13 receptor α2 (IL-13Rα2) on the glioma cells and heparan sulfate on neovascular endothelial cells, we developed a paclitaxel (PTX) loaded Pep-1 and CGKRK peptide-modified PEG-PLGA nanoparticle (PC-NP-PTX) for glioma cells and neovasculature dual-targeted chemotherapy to enhance the antiglioma efficacy. There were significant differences both on the enhancement of cellular uptake in HUVEC and C6 cells and on the improvement of in vitro antiglioma activity in the respect of proliferation, tumor spheroid growth, tube formation, and migration between PC-NP-PTX and Taxol and NP-PTX. As for C6 cells, the IC50 were 3.59 ± 0.056, 2.37 ± 0.044, 1.38 ± 0.028, 1.82 ± 0.035, and 1.00 ± 0.016 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, and for HUVEC cells, the IC50 were 0.44 ± 0.006, 0.33 ± 0.005, 0.25 ± 0.005, 0.19 ± 0.004, and 0.16 ± 0.004 μg/mL of Taxol, NP-PTX, Pep-NP-PTX, CGKRK-NP-PTX, and PC-NP-PTX, respectively. In vivo distribution assays confirmed that PC-NP-PTX targeted and accumulated effectively at glioma site. PC-NP-PTX showed a longer median survival time of 61 days when compared with Taxol (22 days), NP-PTX (24 days), Pep-NP-PTX (32 days), and CGKRK-NP-PTX (34 days). The in vivo antiglioma efficacy and safety evaluation showed PC-NP-PTX significantly enhanced the antiglioma efficacy and displayed negligible acute toxicity.}, number={10}, journal={MOLECULAR PHARMACEUTICS}, author={Lv, Lingyan and Jiang, Yan and Liu, Xin and Wang, Baoyan and Lv, Wei and Zhao, Yue and Shi, Huihui and Hu, Quanyin and Xin, Hongliang and Xu, Qunwei and et al.}, year={2016}, month={Oct}, pages={3506–3517} } @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{shi_xu_ye_song_cheng_di_hu_li_ju_jiang_et al._2016, title={Photo-Cross-Linked Scaffold with Kartogenin-Encapsulated Nanoparticles for Cartilage Regeneration}, volume={10}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.5b06663}, abstractNote={The regeneration of cartilage, an aneural and avascular tissue, is often compromised by its lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), a small molecular compound, can induce bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. The previous in vitro study showed that kartogenin also had a chondrogenesis effect on synovium derived mesenchymal stem cells (SMSCs). Herein, we present the effect of an ultraviolet-reactive, rapidly cross-linkable scaffold integrated with kartogenin-loaded nanoparticles using an innovational one-step technology. In vivo studies showed its potential role for cell homing, especially for recruiting the host's endogenous cells, including BMSCs and SMSCs, without cell transplantation. Of note, the regenerated tissues were close to the natural hyaline cartilage based on the histological tests, specific markers analysis, and biomechanical tests. This innovative KGN release system makes the chondrogenesis efficient and persistent.}, number={1}, journal={ACS NANO}, author={Shi, Dongquan and Xu, Xingquan and Ye, Yanqi and Song, Kai and Cheng, Yixiang and Di, Jin and Hu, Quanyin and Li, Jianxin and Ju, Huangxian and Jiang, Qing and et al.}, year={2016}, month={Jan}, pages={1292–1299} } @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{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_lu_bomba_ye_jiang_isaacson_gu_2016, title={Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots}, volume={16}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.5b04343}, abstractNote={Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.}, number={2}, journal={NANO LETTERS}, author={Hu, Quanyin and Sun, Wujin and Lu, Yue and Bomba, Hunter N. and Ye, Yanqi and Jiang, Tianyue and Isaacson, Ari J. and Gu, Zhen}, year={2016}, month={Feb}, pages={1118–1126} } @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{sun_ji_hall_hu_wang_beisel_gu_2015, title={Self-Assembled DNA Nanoclews for the Efficient Delivery of CRISPR-Cas9 for Genome Editing}, volume={54}, ISSN={1433-7851}, url={http://dx.doi.org/10.1002/ANIE.201506030}, DOI={10.1002/anie.201506030}, abstractNote={Abstract}, number={41}, journal={Angewandte Chemie International Edition}, publisher={Wiley}, author={Sun, Wujin and Ji, Wenyan and Hall, Jordan M. and Hu, Quanyin and Wang, Chao and Beisel, Chase L. and Gu, Zhen}, year={2015}, month={Aug}, pages={12029–12033} } @article{di_kim_hu_jiang_gu_2015, title={Spatiotemporal drug delivery using laser-generated-focused ultrasound system}, volume={220}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2015.08.033}, abstractNote={Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Di, Jin and Kim, Jinwook and Hu, Quanyin and Jiang, Xiaoning and Gu, Zhen}, year={2015}, month={Dec}, pages={592–599} } @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} } @article{hu_katti_gu_2014, title={Enzyme-responsive nanomaterials for controlled drug delivery}, volume={6}, ISSN={["2040-3372"]}, DOI={10.1039/c4nr04249b}, abstractNote={Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.}, number={21}, journal={NANOSCALE}, author={Hu, Quanyin and Katti, Prateek S. and Gu, Zhen}, year={2014}, pages={12273–12286} }