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Here, we identify piR\u20101873 as a cardioprotective piRNA that is down\u2010regulated in MI patients, mouse models, and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010treated cardiomyocytes. Serum piR\u20101873 levels correlated with MI biomarkers, suggesting its potential as a complementary biomarker, with an area under the curve (AUC) of 0.8389. Mechanistically, piR\u20101873 directly targeted Usp2 and inhibited RIP1\/RIP3\/MLKL\u2010mediated necroptosis. To achieve efficient delivery, we developed ultrasound (US)\u2010responsive piRNA nanoparticles (piR\u2010NPs) consisting of a perfluorohexane (PFH) phase\u2010change core loaded with piR\u20101873 and coated with a cardiomyocyte membrane shell. In vitro, piR\u2010NPs enhanced piR\u20101873 delivery and suppressed cardiomyocyte necroptosis, with US further improving these effects. In MI mice, piR\u2010NPs accumulated in infarcted myocardium, and US enhanced nanoparticle retention, resulting in improved cardiac function, reduced fibrosis, and attenuated necroptosis without detectable systemic toxicity. Collectively, this study reveals the diagnostic and therapeutic potential of piR\u20101873 and establishes a biomimetic, US\u2010triggered piRNA delivery platform for MI treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.78282","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:26:41Z","timestamp":1792034801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound\u2010Triggered piRNA Delivery Using Biomimetic Phase\u2010Changeable Nanoparticles for Theranostics of Myocardial Infarction"],"prefix":"10.1002","author":[{"given":"Yajun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiac Ultrasound The Affiliated Hospital of Qingdao University  Qingdao Shandong People's Republic of 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