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Herein, we report a zwitterionic nanogels platform (poly(\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide dimethylaminoethyl methacrylate), PODMMA) that enables precise induction of photopyroptosis via intrinsic mitochondrial targeting. Owing to its unique\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide zwitterionic structure, the PODMMA nanogels exhibit prolonged blood circulation, selective mitochondrial localization without the need for additional targeting ligands, and enhanced tumor accumulation. In vitro studies demonstrate that the drug\u2010loaded nanogels efficiently accumulate in mitochondria. Upon irradiation with a 640\u00a0nm laser (5\u00a0min, 30\u00a0mW\/cm\n                    <jats:sup>2<\/jats:sup>\n                    ), reactive oxygen species (ROS) amplification is triggered leading to the activation of the caspase\u20103\/gasdermin E (GSDME) pyroptosis pathway. In vivo evaluations demonstrate exceptional therapeutic efficacy with 99.3% tumor inhibition and negligible systemic toxicity. This study establishes a versatile strategy for subcellular\u2010targeted photopyroptosis and precision cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/smll.73796","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T16:28:48Z","timestamp":1779035328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondria\u2010Targeted Zwitterionic Nanogels Trigger Photopyroptosis for Enhanced Cancer Therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Yuxin","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular Science Fudan University  Shanghai P. R. 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