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Timely reperfusion following MI unavoidably contributes to additional cardiomyocyte death, a phenomenon known as myocardial ischemia\/reperfusion injury (I\/RI). The surge in free radicals and extensive cardiomyocyte loss significantly promote the progression toward heart failure, a condition that remains a major therapeutic challenge. Development of microRNA (miRNA)\u2010based therapeutics for I\/RI is hindered by poor intracellular delivery of miRNA and its rapid degradation in vivo. Nanozymes with enzyme\u2010mimetic activities offer promising platforms for miRNA delivery while concurrently mitigating oxidative stress. Hollow ceria nanozymes decorated with gold nanoparticles (AuNPs) are developed to deliver miR\u2010486, whose cavernous rooms enable them to accommodate miRNA. Elevated miR\u2010486 expression is shown to suppress myocardial apoptosis and alleviate I\/RI. Equipped with cardiac target peptide, miR\u2010486@CeO\n                    <jats:sub>2<\/jats:sub>\n                    \/Au\u2010pep nanoparticles are integrated with superior enzyme\u2010mimicking functions than a single entity, reactive oxygen species (ROS) scavenging, and improved miR\u2010486 delivery. In myocardial I\/RI mice, miR\u2010486@CeO\n                    <jats:sub>2<\/jats:sub>\n                    \/Au\u2010pep can specifically accumulate at the heart and promote miR\u2010486 to escape from lysosomes, which further boosts the bioactivity of miR\u2010486 in cardiomyocytes. These combined effects confer cardioprotection and inhibit adverse ventricle remodeling. The nanosystem through synergetic works of miRNA and nanozymes provides an effective approach to treating myocardial I\/RI.\n                  <\/jats:p>","DOI":"10.1002\/smll.202502778","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:45:15Z","timestamp":1745815515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cascade Nanozyme Delivering miRNA to Ischemic Heart to Alleviate Myocardial Ischemia\u2010Reperfusion Injury"],"prefix":"10.1002","volume":"21","author":[{"given":"Xuerui","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Geriatrics (Shanghai University) Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) School of Medicine Shanghai University  Nantong 226011 China"},{"name":"Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair Joint International Research 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(The Sixth People's Hospital of Nantong) School of Medicine Shanghai University  Nantong 226011 China"},{"name":"Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education) School of Life Science Shanghai University  Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Geriatrics (Shanghai University) Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) School of Medicine Shanghai University  Nantong 226011 China"},{"name":"Institute of Cardiovascular Sciences Shanghai Engineering Research Center of Organ Repair Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education) School of Life Science Shanghai University  Shanghai 200444 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