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However, current monoclonal antibody targeting CD47\u2010SIRP\u03b1 axis is associated with on\u2010target off\u2010tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano\u2010degrader is developed to inhibit CD47\u2010SIRP\u03b1 axis in a site\u2010specific manner through SIRP\u03b1 degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano\u2010degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high\u2010affinity binding capability to SIRP\u03b1 on macrophages without signaling capacity. RLP would bind with SIRP\u03b1 and induce its lysosomal degradation through receptor\u2010mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47\u2010SIRP\u03b1 axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano\u2010degrader efficiently degraded SIRP\u03b1 in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.<\/jats:p>","DOI":"10.1002\/advs.202306388","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:40:06Z","timestamp":1710319206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Biomimetic Nano\u2010Degrader Based CD47\u2010SIRP\u03b1 Immune Checkpoint Inhibition Promotes Macrophage Efferocytosis for Cardiac Repair"],"prefix":"10.1002","volume":"11","author":[{"given":"Jinfeng","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhongshan Hospital Fudan University Shanghai Institute of Cardiovascular Diseases  Shanghai 20032 China"},{"name":"National Clinical Research Center for Interventional Medicine Shanghai Clinical Research Center for Interventional Medicine  180 Feng Lin Road Shanghai 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