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Following myocardial reperfusion, S100A8\/A9 molecules are considered pivotal in initiating and regulating tissue inflammatory damage. Effectively reducing the S100A8\/A9 level in ischemic myocardial tissue holds significant therapeutic value in salvaging damaged myocardium. In this study, HA (hemagglutinin)\u2010 and RAGE (receptor for advanced glycation end products)\u2010 comodified macrophage membrane\u2010coated siRNA nanoparticles (MMM\/RNA NPs) with siRNA targeting S100A9 (S100A9\u2010siRNA) are successfully prepared. This nanocarrier system is able to target effectively the injured myocardium in an inflammatory environment while evading digestive damage by lysosomes. In vivo, migration of MMM\/RNA NPs to myocardial injury lesions is confirmed in a myocardial ischemia\u2010reperfusion injury (MIRI) mouse model. Intravenous injection of MMM\/RNA NPs significantly reduced S100A9 levels in serum and myocardial tissues, further decreasing myocardial infarction area and improving cardiac function. Targeted reduction of S100A8\/A9 by genetically modified macrophage membrane\u2010coated nanoparticles may represent a new therapeutic intervention for MIRI.<\/jats:p>","DOI":"10.1002\/advs.202403542","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T11:16:31Z","timestamp":1726139791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Engineered Macrophage Membrane\u2010Coated S100A9\u2010siRNA for Ameliorating Myocardial Ischemia\u2010Reperfusion Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"He","family":"Lu","sequence":"first","affiliation":[{"name":"Nanjing Drum Tower Hospital Drum Tower Clinical College Nanjing University of Chinese Medicine  No. 321 Zhongshan Road Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Drum 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