@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} } @misc{lee_goudie_tebon_sun_luo_lee_zhang_fetah_kim_xue_et al._2020, title={Non-transdermal microneedles for advanced drug delivery}, volume={165-166}, ISSN={["1872-8294"]}, DOI={10.1016/j.addr.2019.11.010}, abstractNote={Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Lee, KangJu and Goudie, Marcus J. and Tebon, Peyton and Sun, Wujin and Luo, Zhimin and Lee, Junmin and Zhang, Shiming and Fetah, Kirsten and Kim, Han-Jun and Xue, Yumeng and et al.}, year={2020}, pages={41–59} } @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{ye_wang_sun_bomba_gu_2019, title={Topical and Transdermal Nanomedicines for Cancer Therapy}, volume={5}, ISBN={["978-3-030-01773-6"]}, ISSN={["2364-1126"]}, DOI={10.1007/978-3-030-01775-0_10}, abstractNote={Topical and transdermal nanomedicine systems have attracted considerable attention in anticancer therapy. The administration route toward the skin can transport active drugs through the skin barrier and control their entrance into the blood circulation system. Agents delivered through this platform are capable of escaping the first pass of metabolism, which causes physiological degradation of the agent and systemic clearance. Apart from methodology to facilitate the delivery of drug transdermally, the formulation of nanomedicines to preserve the therapeutic’s property is also critical for overall clinical outcomes. This strategy improves the efficiency of encapsulated drugs by potentiating the targeting capability and tailoring the release kinetics toward specific tumors. This chapter summarizes the principles and the recent innovations in the field of transdermal nanomedicine together with opportunities and challenges in clinical translation. For the continued development of novel transdermal devices incorporating nanotechnology, a deeper understanding is required in rational nanoparticle design and their pharmacokinetics.}, journal={NANOTHERANOSTICS FOR CANCER APPLICATIONS}, author={Ye, Yanqi and Wang, Jinqiang and Sun, Wujin and Bomba, Hunter N. and Gu, Zhen}, year={2019}, pages={231–251} } @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{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{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{wang_zhuang_cheng_sun_wu_chen_ying_2017, title={In vivo multienzyme complex coconstruction of N-Acetylneuraminic acid lyase and N-Acetylglucosamine-2-epimerase for Biosynthesis of N-Acetylneuraminic acid}, volume={65}, number={34}, journal={Journal of Agricultural and Food Chemistry}, author={Wang, Z. F. and Zhuang, W. and Cheng, J. and Sun, W. J. and Wu, J. L. and Chen, Y. and Ying, H. J.}, year={2017}, pages={7467–7475} } @article{yu_zhang_sun_kahkoska_wang_buse_gu_2017, title={Insulin-responsive glucagon delivery for prevention of hypoglycemia}, volume={13}, DOI={10.1002/smll.201770108}, abstractNote={In article number 1603028, by Zhen Gu and co-workers, an insulin-responsive glucagon delivery device based on a microneedle (MN)-array patch is developed. Utilizing hyperinsulinemia as a dangerous signal, this “smart glucagon patch” can release glucagon to reduce the risk of hypoglycemia during diabetes management.}, number={19}, journal={Small (Weinheim An Der Bergstrasse, Germany)}, author={Yu, J. C. and Zhang, Y. Q. and Sun, W. J. and Kahkoska, A. R. and Wang, J. Q. and Buse, J. B. and Gu, Z.}, year={2017} } @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{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} } @misc{sun_gu_2017, title={Tailoring non-viral delivery vehicles for transporting genome-editing tools}, volume={60}, DOI={10.1007/s40843-016-5154-4}, abstractNote={The CRISPR-Cas system, especially the type II CRISPR-Cas9 system from Streptococcuspyogenes, has rapidly emerged as a popular genome editing tool. The development of Cas9 derivatives further expanded the toolbox of CRISPRCas9 based genome editing kit. However, therapeutic translation of the CRISPR-Cas9 system in vivo is severely impeded by the absence of an appropriate delivery carrier. The complexity and high molecular weight of the CRISPR-Cas9 system, together with the physiological barriers for nucleus targeted cargo transportation have made it a huge challenge for in vivo therapeutic CRISPR-Cas9 delivery. Currently, the main stream carriers for systemic delivery of CRISPR-Cas9 are viral based, such as adeno-associated virus. However, the safety concerns surrounding viral vectors call for the development of non-viral nanocarriers. In this review, we survey the recent advances in the development of non-viral delivery systems for CRISPR-Cas9. Challenges and future directions in this field are also discussed.}, number={6}, journal={Science China-Materials}, author={Sun, W. J. and Gu, Z.}, year={2017}, pages={511–515} } @article{sun_gu_2016, title={ATP-Responsive Drug Delivery Systems}, volume={13}, ISSN={["1744-7593"]}, DOI={10.1517/17425247.2016.1140147}, abstractNote={Advances in material science brought about a wide range of drug delivery systems, from traditional bulk controlled release formulations to modern nanotechnology based carriers, for improved drug efficacy. A wide collection of nanoparticle frameworks, like metallic nanoparticles, liposomes, polymeric nanogels, protein or DNA nanoassemblies, were employed in constructing nanocarriers. Basic nanoparticle framework can be viewed as the chassis of a motor vehicle, upon which various functional modules could be installed, such as targeting ligands for vehicle “steering”, drug binding and environment-sensing moieties for cargo loading and unloading. Uncontrolled drug release from nanocarriers along their way to diseased areas significantly compromises the therapeutic effects while increasing the risk of side effects. The concept of “on-demand” therapeutics would be more promising when the nanocarriers are “smart” to perceive their surrounding environment and react correspondingly. To generate these “smart” formulations for precise delivery, numerous types of stimuli-responsive materials were developed and incorporated into the nanocarriers [1]. Our group has been devoted to the development of “smart” nanocarriers responsive to a variety of triggers for cancer and diabetes treatment. For example, external physical triggers, like focused ultrasound [2] or tensile strains [3] were applied as hints to control drug dosing. Internal physiological triggers, like overexpressed enzymes (such as furin [4] or hyaluronidase [5]), acidic environment [6], reducing gradients [7], hypoxia [8] or elevated blood glucose levels [9] were also harnessed for controlling drug release. In this editorial, we discuss an emerging strategy utilizing the “molecular unit of currency” in biological energy transfer - ATP - as a trigger for therapeutic delivery. The sharp concentration contrast between extracellular (<0.4 mM) and intracellular (1-10 mM) environments makes ATP a feasible cue for regulating drug release [5].}, number={3}, journal={EXPERT OPINION ON DRUG DELIVERY}, author={Sun, Wujin and Gu, Zhen}, year={2016}, month={Mar}, pages={311–314} } @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} } @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{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} } @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{mo_jiang_sun_gu_2015, title={ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery}, volume={50}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2015.01.053}, abstractNote={Stimuli-triggered drug delivery systems are primarily focused on the applications of the tumor microenvironmental or cellular physiological cues to enhance the release of drugs at the target site. In this study, we applied adenosine-5′-triphosphate (ATP), the primary “energy molecule”, as a trigger for enhanced release of preloaded drugs responding to the intracellular ATP concentration that is significantly higher than the extracellular level. A new ATP-responsive anticancer drug delivery strategy utilizing DNA-graphene crosslinked hybrid nanoaggregates as carriers was developed for controlled release of doxorubicin (DOX), which consists of graphene oxide (GO), two single-stranded DNA (ssDNA, denoted as DNA1 and DNA2) and ATP aptamer. The single-stranded DNA1 and DNA2 together with the ATP aptamer serve as the linkers upon hybridization for controlled assembly of the DNA-GO nanoaggregates, which effectively inhibited the release of DOX from the GO nanosheets. In the presence of ATP, the responsive formation of the ATP/ATP aptamer complex causes the dissociation of the aggregates, which promoted the release of DOX in the environment with a high ATP concentration such as cytosol compared with that in the ATP-deficient extracellular fluid. This supports the development of a novel ATP-responsive platform for targeted on-demand delivery of anticancer drugs inside specific cells.}, journal={BIOMATERIALS}, author={Mo, Ran and Jiang, Tianyue and Sun, Wujin and Gu, Zhen}, year={2015}, month={May}, pages={67–74} } @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{ji_sun_feng_song_zhang_ouyang_gu_xie_2015, title={Characterization of a novel N-acetylneuraminic acid lyase favoring N-acetylneuraminic acid synthesis}, volume={5}, ISSN={["2045-2322"]}, DOI={10.1038/srep09341}, abstractNote={Abstract}, journal={SCIENTIFIC REPORTS}, author={Ji, Wenyan and Sun, Wujin and Feng, Jinmei and Song, Tianshun and Zhang, Dalu and Ouyang, Pingkai and Gu, Zhen and Xie, Jingjing}, year={2015}, month={Mar} } @misc{sun_gu_2015, title={Engineering DNA scaffolds for delivery of anticancer therapeutics}, volume={3}, ISSN={["2047-4849"]}, DOI={10.1039/c4bm00459k}, abstractNote={DNA scaffolds with programmability in size, shape and surface chemistry have been engineered for the delivery of various anticancer therapeutics.}, number={7}, journal={BIOMATERIALS SCIENCE}, author={Sun, Wujin and Gu, Zhen}, year={2015}, pages={1018–1024} } @article{yu_zhang_ye_disanto_sun_ranson_ligler_buse_gu_2015, title={Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery}, volume={112}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1505405112}, abstractNote={Significance}, number={27}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Yu, Jicheng and Zhang, Yuqi and Ye, Yanqi and DiSanto, Rocco and Sun, Wujin and Ranson, Davis and Ligler, Frances S. and Buse, John B. and Gu, Zhen}, year={2015}, month={Jul}, pages={8260–8265} } @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{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{sun_lu_gu_2014, title={Advances in Anticancer Protein Delivery using Micro-/Nanoparticles}, volume={31}, ISSN={["1521-4117"]}, DOI={10.1002/ppsc.201400140}, abstractNote={Proteins exhibiting anticancer activities, especially those capable of discriminately killing cancer cells, have attracted increasing interest in developing protein‐based anticancer therapeutics. This Progress Report surveys recent advances in delivering anticancer proteins directly to tumor tissue for inducing apoptosis/necrosis or indirectly to antigen presenting cells for provoking immune responses. Protein delivery carriers such as inorganic particles, lipid particles, polymeric particles, DNA/protein‐based biomacromolecular particles, as well as cell based carriers are reviewed with comments on their advantages and limitations. Future challenges and opportunities are also discussed.}, number={12}, journal={PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION}, author={Sun, Wujin and Lu, Yue and Gu, Zhen}, year={2014}, month={Dec}, pages={1204–1222} } @article{sun_jiang_lu_reiff_mo_gu_2014, title={Cocoon-Like Self-Degradable DNA Nanoclew for Anticancer Drug Delivery}, volume={136}, ISSN={["0002-7863"]}, DOI={10.1021/ja5088024}, abstractNote={A bioinspired cocoon-like anticancer drug delivery system consisting of a deoxyribonuclease (DNase)-degradable DNA nanoclew (NCl) embedded with an acid-responsive DNase I nanocapsule (NCa) was developed for targeted cancer treatment. The NCl was assembled from a long-chain single-stranded DNA synthesized by rolling-circle amplification (RCA). Multiple GC-pair sequences were integrated into the NCl for enhanced loading capacity of the anticancer drug doxorubicin (DOX). Meanwhile, negatively charged DNase I was encapsulated in a positively charged acid-degradable polymeric nanogel to facilitate decoration of DNase I into the NCl by electrostatic interactions. In an acidic environment, the activity of DNase I was activated through the acid-triggered shedding of the polymeric shell of the NCa, resulting in the cocoon-like self-degradation of the NCl and promoting the release of DOX for enhanced therapeutic efficacy.}, number={42}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Sun, Wujin and Jiang, Tianyue and Lu, Yue and Reiff, Margaret and Mo, Ran and Gu, Zhen}, year={2014}, month={Oct}, pages={14722–14725} } @article{zhu_sun_wang_meng_zhang_guo_ouyang_ying_xie_2014, title={Engineered cytidine triphosphate synthetase with reduced product inhibition}, volume={27}, number={7}, journal={Protein Engineering Design & Selection}, author={Zhu, M. Z. and Sun, W. J. and Wang, Y. and Meng, J. and Zhang, D. L. and Guo, T. and Ouyang, P. K. and Ying, H. J. and Xie, J. J.}, year={2014}, pages={225–233} } @article{lu_mo_tai_sun_pacardo_qian_shen_ligler_gu_2014, title={Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc07004f}, abstractNote={Self-folded redox/acid dual-responsive nanocarriers (RAD-NCs) are developed for physiologically triggered delivery of anticancer drugs. The evidenced redox/acid responsiveness, facile decoration of ligands, and active tumor-targeting capability of RAD-NCs suggest their potential as a promising formulation for tumor-targeted chemotherapy.}, number={95}, journal={CHEMICAL COMMUNICATIONS}, author={Lu, Yue and Mo, Ran and Tai, Wanyi and Sun, Wujin and Pacardo, Dennis B. and Qian, Chenggen and Shen, Qundong and Ligler, Frances S. and Gu, Zhen}, year={2014}, pages={15105–15108} } @article{jiang_sun_zhu_burns_khan_mo_gu, title={Furin-mediated sequential delivery of anticancer cytokine and small-molecule drug shuttled by graphene}, volume={27}, number={6}, journal={Advanced Materials}, author={Jiang, T. Y. and Sun, W. J. and Zhu, Q. W. and Burns, N. A. and Khan, S. A. and Mo, R. and Gu, Z.}, pages={1021–1028} }