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Here, we develop a spatiotemporally precise therapeutic strategy using mitochondria\u2010targeted photodynamic microneedles (\n                    <jats:italic>mito<\/jats:italic>\n                    TPS\u2010MNs) to orchestrate GSDME\u2010mediated pyroptosis and potentiate systemic immunoradiotherapy. Upon transdermal photoactivation,\n                    <jats:italic>mito<\/jats:italic>\n                    TPS induces intense, mitochondria\u2010confined reactive oxygen species (ROS) bursts, triggering a caspase\u20103\/GSDME\u2010dependent pyroptotic cascade while simultaneously disrupting mitochondrial respiration to alleviate tumor hypoxia. This dual\u2010action mechanism sensitizes melanoma to x\u2010ray irradiation, achieving near\u2010complete regression of primary tumors and remodeling \u201ccold\u201d tumor microenvironments into immunologically \u201chot\u201d niches. The explosive release of damage\u2010associated molecular patterns (DAMPs) from pyroptotic cells functions as an in situ cancer vaccine, promoting dendritic cell maturation, the systemic recruitment of CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes, and potent abscopal responses against untreated distant metastases. Our work establishes mitochondria\u2010directed pyroptosis as a mechanistic switch to bypass the inherent apoptotic resistance of melanoma, providing a clinically translatable strategy to convert localized interventions into systemic immunity against advanced melanoma.\n                  <\/jats:p>","DOI":"10.1002\/adma.74638","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:39:35Z","timestamp":1787038775000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondria\u2010Targeted Pyroptosis Orchestrated by Photodynamic Microneedle Patches Potentiates Melanoma Immunoradiotherapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Ziyao","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Jiangsu Key Laboratory of Radiation Injury Prevention and Hazardous Substance Control Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"He","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Jiangsu Key Laboratory of Radiation Injury Prevention and Hazardous Substance Control Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou 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Protection School of Radiation Medicine and Protection Jiangsu Key Laboratory of Radiation Injury Prevention and Hazardous Substance Control Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Bu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-3376","authenticated-orcid":false,"given":"Hengte","family":"Ke","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabing","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery of the First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1024","authenticated-orcid":false,"given":"Kai","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Jiangsu Key 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