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However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK \uff08main effector receptor), and overexpression of \u201cdo not eat me\u201d signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post\u2010MI\/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Herein, inspired by the application research of chimeric antigen receptor macrophages (CAR\u2010Ms) in solid tumors, a genetically modified macrophage\u2010based synergistic drug delivery strategy that effectively challenging the three major barriers in an integrated manner is developed. This strategy involves the overexpression of exogenous macrophages with CCR2 (C\u2010C chemokine receptor type 2) and cleavage\u2010resistant MerTK, as well as surface clicking with liposomal PEP\u201020 (a CD47 antagonist). In MI\/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. This therapy focuses on inhibiting the initiation and promoting active resolution of inflammation, providing new insights for immune\u2010regulatory therapy.<\/jats:p>","DOI":"10.1002\/adhm.202303267","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T13:40:56Z","timestamp":1704894056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Genetically Engineered Macrophages Co\u2010Loaded with CD47 Inhibitors Synergistically Reconstruct Efferocytosis and Improve Cardiac Remodeling Post Myocardial Ischemia Reperfusion Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Haipeng","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhongshan Hospital, Fudan University Shanghai Institute of Cardiovascular Diseases  Shanghai 20032 P. R. 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