@article{hu_li_shen_zhu_huang_su_dinh_cores_cheng_2021, title={Exosome-eluting stents for vascular healing after ischaemic injury}, volume={5}, ISSN={["2157-846X"]}, url={https://doi.org/10.1038/s41551-021-00705-0}, DOI={10.1038/s41551-021-00705-0}, abstractNote={Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair. Exosome-eluting stents implanted in rats after ischaemic injury accelerate vascular healing and promote tissue regeneration.}, number={10}, journal={NATURE BIOMEDICAL ENGINEERING}, publisher={Springer Science and Business Media LLC}, author={Hu, Shiqi and Li, Zhenhua and Shen, Deliang and Zhu, Dashuai and Huang, Ke and Su, Teng and Dinh, Phuong-Uyen and Cores, Jhon and Cheng, Ke}, year={2021}, month={Oct}, pages={1174–1188} } @article{liang_li_ren_jia_guo_li_zhang_hu_zhu_shen_et al._2020, title={Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis}, volume={13}, ISSN={["1998-0000"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85086369757&partnerID=MN8TOARS}, DOI={10.1007/s12274-020-2833-6}, number={8}, journal={NANO RESEARCH}, author={Liang, Hongxia and Li, Zhenhua and Ren, Zhigang and Jia, Qiaodi and Guo, Linna and Li, Shasha and Zhang, Hongyu and Hu, Shiqi and Zhu, Dashuai and Shen, Deliang and et al.}, year={2020}, month={Aug}, pages={2197–2202} } @article{qiao_hu_huang_su_li_vandergriff_cores_dinh_allen_shen_et al._2020, title={Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs}, volume={10}, ISSN={["1838-7640"]}, DOI={10.7150/thno.39434}, abstractNote={Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.}, number={8}, journal={THERANOSTICS}, author={Qiao, Li and Hu, Shiqi and Huang, Ke and Su, Teng and Li, Zhenhua and Vandergriff, Adam and Cores, Jhon and Dinh, Phuong-Uyen and Allen, Tyler and Shen, Deliang and et al.}, year={2020}, pages={3474–3487} } @article{shen_li_hu_huang_su_liang_liu_cheng_2019, title={Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells}, volume={19}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.8b04970}, abstractNote={Stem cell therapies have shown promise in treating acute and chronic ischemic heart disease. However, current therapies are limited by the low retention and poor integration of injected cells in the injured tissue. Taking advantage of the natural infarct-homing ability of platelets, we engineered CD34 antibody-linked platelets (P-CD34) to capture circulating CD34-positive endogenous stem cells and direct them to the injured heart. In vitro, P-CD34 could bind to damaged aortas and capture endogenous stem cells in whole blood. In a mouse model of acute myocardial infarction, P-CD34 accumulated in the injured heart after intravenous administration, leading to a concentration of endogenous CD34 stem cells in the injured heart for effective heart repair. This represents a new technology for endogenous stem cell therapy.}, number={3}, journal={NANO LETTERS}, author={Shen, Deliang and Li, Zhenhua and Hu, Shiqi and Huang, Ke and Su, Teng and Liang, Hongxia and Liu, Feiran and Cheng, Ke}, year={2019}, month={Mar}, pages={1883–1891} } @article{huang_li_su_shen_hu_cheng_2019, title={Bispecific Antibody Therapy for Effective Cardiac Repair through Redirection of Endogenous Stem Cells}, volume={2}, ISSN={["2366-3987"]}, DOI={10.1002/adtp.201900009}, abstractNote={AbstractBone marrow stem cells (BMSCs) are a promising strategy for cardiac regenerative therapy for myocardial infarction (MI). However, cell transplantation has to overcome a number of hurdles, such as cell quality control, clinical practicality, low cell retention/engraftment, and immune reactions when allogeneic cells are used. Bispecific antibodies (BsAbs) have been developed as potential agents in cancer immunotherapy but their application is sparse in cardiovascular diseases. In the present study, BsAbs are designed by chemical cycloaddition of F(ab′)2 fragments from monoclonal anti‐CD34 and anti‐ cardiac myosin heavy chain (CMHC) antibodies, which specifically targets circulating CD34‐positive cells and injured cardiomyocytes simultaneously. It is hypothesized that intravenous administration of stem cell re‐directing (SCRD) BsAbs (anti‐CD34‐F(ab′)2–anti‐CMHC‐F(ab′)2) can home endogenous BMSCs to the injured heart for cardiac repair. The in vivo studies in a mouse model with heart ischemia/reperfusion (I/R) injury demonstrate the safety and therapeutic potency of SCRD BsAb, which supports cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function.}, number={10}, journal={ADVANCED THERAPEUTICS}, author={Huang, Ke and Li, Zhenhua and Su, Teng and Shen, Deliang and Hu, Shiqi and Cheng, Ke}, year={2019}, month={Oct} } @article{su_huang_ma_liang_dinh_chen_shen_allen_qiao_li_et al._2019, title={Platelet-Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury}, volume={29}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.201803567}, abstractNote={AbstractCardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post‐heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post‐ischemic recovery. A platelet‐inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE2)‐modified platelet membrane and cardiac stromal cell‐secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct‐homing ability of platelet membrane and the overexpression of PGE2 receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE2/EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.}, number={4}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Su, Teng and Huang, Ke and Ma, Hong and Liang, Hongxia and Dinh, Phuong-Uyen and Chen, Justin and Shen, Deliang and Allen, Tyler A. and Qiao, Li and Li, Zhenhua and et al.}, year={2019}, month={Jan} } @article{li_shen_hu_su_huang_liu_hou_cheng_2018, title={Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair}, volume={12}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.8b05892}, abstractNote={Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h). Through bioorthogonal click reaction, the two antibodies are linked in vivo, engaging endogenous stem cells with circulating platelets. As a result, the platelets redirect the stem cells to the injured heart. In vitro and in vivo studies demonstrated that bioorthogonal click reaction was able to induce the conjugation of platelets and endothelial progenitor cells (EPCs) and enhance the binding of EPCs to collagen and injured blood vessels. More importantly, in a mouse model of acute myocardial infarction, the in vivo results of cardiac function, heart morphometry, and immunohistochemistry assessment all confirmed effective heart repair by the PTBC system.}, number={12}, journal={ACS NANO}, author={Li, Zhenhua and Shen, Deliang and Hu, Shiqi and Su, Teng and Huang, Ke and Liu, Feiran and Hou, Lei and Cheng, Ke}, year={2018}, month={Dec}, pages={12193–12200} } @article{tang_su_huang_dinh_wang_vandergriff_hensley_cores_allen_li_et al._2018, title={Targeted repair of heart injury by stem cells fused with platelet nanovesicles}, volume={2}, ISSN={2157-846X}, url={http://dx.doi.org/10.1038/s41551-017-0182-x}, DOI={10.1038/s41551-017-0182-x}, abstractNote={Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types. The attachment of platelet nanovesicles to the surface of cardiac stem cells increases the retention of the cells delivered to the heart and reduces infarct size in rat and pig models of acute myocardial infarction.}, number={1}, journal={Nature Biomedical Engineering}, publisher={Springer Science and Business Media LLC}, author={Tang, Junnan and Su, Teng and Huang, Ke and Dinh, Phuong-Uyen and Wang, Zegen and Vandergriff, Adam and Hensley, Michael T. and Cores, Jhon and Allen, Tyler and Li, Taosheng and et al.}, year={2018}, month={Jan}, pages={17–26} }