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However, whether ROS\u2010driven stress also reprograms tumor immune signaling toward immune resistance, thereby limiting durable antitumor immunity, remains unclear. This study reveals that immune resistance is a universal mechanism shared by three major classes of clinically used SDT sensitizers. A porphyrin\u2010biguanide\u2010loaded albumin nanoparticle (POR\u2010BG@Alb) is rationally developed as a self\u2010immunoregulatory sonosensitizer, which induces mitochondrial dysfunction to activate AMP\u2010activated protein kinase (AMPK) and suppress c\u2010MYC, concomitantly downregulating PD\u2010L1 and CD47 and enhancing T\u2010cell killing and macrophage phagocytosis. Unlike clinically used traditional sensitizers that upregulate PD\u2010L1\/CD47 after SDT and promote innate and adaptive immunosuppression, POR\u2010BG@Alb amplifies sonodynamic efficacy while limiting this feedback. Across orthotopic bladder cancer, subcutaneous xenograft, and orthotopic breast cancer models, POR\u2010BG@Alb\u2010mediated SDT suppresses primary tumors, elicits abscopal antimetastatic effects, establishes immune memory, and extends median survival in subcutaneous xenografts from 17 to 44 days. Collectively, this research unmasks a previously unappreciated role of SDT in inducing immune resistance and shows that POR\u2010BG@Alb integrates potent sonodynamic activity with self\u2010oxygen regulation and self\u2010immunoregulation to enable durable systemic antitumor immunity, providing a promising nanotherapeutic strategy for SDT clinical translation.<\/jats:p>","DOI":"10.1002\/adma.73775","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:41:12Z","timestamp":1781934072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Self\u2010Immunoregulatory Nanosensitizer for Sonodynamic Cancer Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Jiahao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology The Third Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"Zhejiang Key Laboratory of Ophthalmic Drug 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