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This limitation underscores the urgent need for innovative treatments that enhance immunogenicity. In this study, an ultrasound (US)\u2010activated nano\u2010oncolytic system (designated as cRGD\u2010Lip@PFP), is presented and consists of nanoliposomes (Lip) modified with the cRGD peptide for targeted tumor delivery. This system features a perfluoropentane (PFP) core that undergoes US\u2010triggered acoustomechanical effects, enabling controlled expansion from nanoscale to microscale, ultimately leading to rupture and the generation of cavitation effects. Intracellular cavitation further induces necroptosis\u2010like oncolytic cell death. The efficacy of various treatments in stimulating immune responses is systematically compared and it is demonstrated that the nano\u2010oncolytic system effectively enhances the release of damage\u2010associated molecular patterns (DAMPs). Additionally, the release of DNA fragments activates the cGAS\u2010STING pathway, resulting in an amplified immune response. Furthermore, this nano\u2010oncolytic system alleviates the hypoxic tumor microenvironment and counteracts immunosuppression. Compared to traditional apoptosis, the necroptosis\u2010like oncolytic cell death induced by this strategy exhibits enhanced immunogenicity. This approach presents an innovative paradigm for tumor immunotherapy based on acoustomechanical effects, offering a promising alternative to tackle the issue of insufficient immunogenicity often associated with conventional apoptosis therapies.<\/jats:p>","DOI":"10.1002\/adma.202508681","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T11:02:11Z","timestamp":1751194931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Breaking Apoptosis\u2010Induced Immune Silence: Ultrasound\u2010Activated Nano\u2010Oncolytic Therapy Reinvigorates Antitumor Immunity"],"prefix":"10.1002","volume":"37","author":[{"given":"Mingxiao","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Ultrasound The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 P. R. 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