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Reactive oxygen species (ROS) play a key role in the pathological progression of MI. The levels and effects of ROS are significantly different in three unique pathological stages of MI, and most antioxidants cannot make corresponding adjustments to eliminate ROS, which leads to a great compromise to treat MI with antioxidants. Herein, an innovative self\u2010sustaining antioxidant strategy is developed to treat MI with self\u2010sustaining selenium\u2010embedded nanoparticles (SSSe NPs). SSSe NPs possess unique self\u2010sustaining antioxidant effects at different pathological stages of MI. This strategy of on\u2010demand ROS elimination during different pathological stages demonstrated excellent MI treatment efficacy and effectively reversed heart failure to normal heart function. The therapeutic mechanism of SSSe NPs is intensively investigated through a series of experiments and mainly involved five critical aspects of myocardial repair: protecting mitochondria, reducing cardiomyocyte apoptosis and ferroptosis, reducing inflammation and fibrosis, and promoting angiogenesis. This strategy not only provides a promising treatment option for MI but also offers inspiration for other ischemic diseases.<\/jats:p>","DOI":"10.1002\/advs.202204999","type":"journal-article","created":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T22:59:06Z","timestamp":1672009146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["A Self\u2010Sustaining Antioxidant Strategy for Effective Treatment of Myocardial Infarction"],"prefix":"10.1002","volume":"10","author":[{"given":"Quan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine Coronary Circulation Center Xiangya Hospital Central South University  Changsha Hunan P.R. China"},{"name":"National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University  Changsha Hunan P.R. 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