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Herein, a mannan\u2010based nanomedicine, Que@MOF\/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti\u2010inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF\/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post\u2010MI, in vivo, administration of Que@MOF\/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF\/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation\u2010targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.<\/jats:p>","DOI":"10.1002\/advs.202308910","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T19:39:13Z","timestamp":1712432353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Inflammation\u2010Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment"],"prefix":"10.1002","volume":"11","author":[{"given":"Danrong","family":"Hu","sequence":"first","affiliation":[{"name":"Rehabilitation Medicine Center and Institute of Rehabilitation Medicine Key Laboratory of Rehabilitation Medicine in Sichuan Province State Key Laboratory of Biotherapy and Cancer Center West China Hospital Collaborative Innovation Center Sichuan University  Chengdu Sichuan 610041 P. 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