Affiliation:
1. Institute of Geriatrics (Shanghai University) Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) School of Medicine Shanghai University Nantong 226011 China
2. Cardiac Regeneration and Ageing Lab Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair School of Life Science Shanghai University Shanghai 200444 China
3. Division of Cardiology, Department of Medicine Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
Abstract
AbstractMyocardial ischemia/reperfusion injury (I/RI) may potentiate cardiac remodeling and heart failure, while effective therapies for I/RI remain lacking. Circulating human plasma‐derived extracellular vesicles (hEV) have great potential to protect against I/RI. However, the effective delivery of hEV in vivo remains a limiting factor for clinical application. The present study constructs a biomimetic delivery system of platelet membrane‐fused hEV (P‐hEV), utilizing the natural affinity of platelets for hEV delivery to the injured vascular and myocardial sites. The results show that platelet membrane and hEV membrane fusion can be achieved through repeated extrusion. Compared to non‐modified hEV, P‐hEV uptake is greatly enhanced in human umbilical vein endothelial cells (HUVECs) stressed by oxygen‐glucose deprivation/reperfusion (OGD/R). Functionally, P‐hEV inhibits HUVEC and neonatal rat cardiomyocyte (NRCM) apoptosis and promotes HUVECs migration and tube formation under OGD/R stress in vitro. Intravenous delivery of P‐hEV more effectively targets and accumulates at injury sites in the heart. Furthermore, P‐hEV significantly enhances protection against acute I/RI and attenuates cardiac remodeling at three weeks post‐I/RI. In conclusion, the platelet membrane‐fused hEV delivery system enhances the target delivery of EV to protect against myocardial I/RI, presenting a novel drug delivery system for ischemic heart diseases.
Funder
Science and Technology Commission of Shanghai Municipality
National Natural Science Foundation of China
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
8 articles.
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