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T cells play an important role in ICI\u2010induced cardiac injury. The inhibition of local T\u2010cell activity is considered an effective strategy for alleviating ICI\u2010related cardiotoxicity. Tumor\u2010derived extracellular vesicles (EVs) contribute to immunosuppression via PD\u2010L1 overexpression. In this study, a bioorthogonal metabolic engineering\u2013driven EV redirecting (Biomeder) strategy for in situ engineered EVs with myocardial\u2010targeting peptides is developed. Accumulated tumor\u2010derived EV (TuEVs) reverses the immune environment in the heart by increasing PD\u2010L1 levels in cardiomyocytes and\/or by directly inhibiting T\u2010cell activity. More importantly, it is found that the redirection of TuEVs further disrupts immunosuppression in tumors, which facilitates anti\u2010tumor activity. Thus, redirecting TuEVs to the heart simultaneously enhances the antitumor efficacy and safety of ICI\u2010based therapy. Furthermore, the Biomeder strategy is successfully expanded to prevent ICI\u2010induced type 1 diabetes. This Biomeder technique is a universal method for the treatment of various ICI\u2010related adverse events.<\/jats:p>","DOI":"10.1002\/adma.202412340","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:50:43Z","timestamp":1727063443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Reversing Immune Checkpoint Inhibitor\u2013Associated Cardiotoxicity via Bioorthogonal Metabolic Engineering\u2013Driven Extracellular Vesicle Redirecting"],"prefix":"10.1002","volume":"36","author":[{"given":"Miao","family":"Fan","sequence":"first","affiliation":[{"name":"The Tenth Affiliated Hospital Southern Medical University (Dongguan People's Hospital)  Dongguan 523059 China"},{"name":"College of Chemistry &amp; Materials Science Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education State Key Laboratory of New Pharmaceutical Preparations and Excipients Chemical Biology Key Laboratory of Hebei Province Hebei University  Baoding 071002 China"},{"name":"College of Pharmacy Hebei Medical University  Shijiazhuang 050017 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry &amp; 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