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Here, a platelet (PLT) membrane nanocarrier (PL720) that encapsulates L\u2010arginine and FTY720 to facilitate the cascade\u2010targeted delivery of these substances to the myocardial injury site and enable the controlled release of L\u2010arginine and FTY720 is developed. Such an innovative approach shows enhanced cardioprotection through multiple target strategies involved in ischemia\u2013reperfusion injury and late reperfusion inflammation. During the ischemia\u2013reperfusion phase, PL720 targets and accumulates in damaged coronary arteries. PL720 rapidly releases L\u2010arginine, stimulating endothelial cells to produce NO, thereby dilating blood vessels and promoting blood flow recovery, while FTY720's sustained release exerts anti\u2010apoptotic effects. During the late reperfusion inflammatory phase, PL720 is captured by circulating inflammatory monocytes and transported into a deeper ischemic myocardial lesion. PL720 promotes macrophage polarization and accelerates the inflammatory repair. Furthermore, the issue of bradycardia associated with the clinical use of FTY720 is innovatively relieved. Therefore, PL720 is a vascular injury and inflammation dual targeting strategy, exhibiting significant potential for multi\u2010targeted therapy and clinical translation for cardiac injury.<\/jats:p>","DOI":"10.1002\/advs.202308727","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T07:53:40Z","timestamp":1707724420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Platelet Membrane Nanocarriers Cascade Targeting Delivery System to Improve Myocardial Remodeling Post Myocardial Ischemia\u2013Reperfusion Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Xuan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Affiliated to Southeast University  87, Dingjiaqiao Nanjing 210009 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxi","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical Engineering Southeast University  Nanjing 210096 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Affiliated to Southeast University  87, Dingjiaqiao Nanjing 210009 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongda Hospital Affiliated to Southeast University  87, Dingjiaqiao Nanjing 210009 P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-6348","authenticated-orcid":false,"given":"Fang","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical Engineering Southeast University  Nanjing 210096 P. R. 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