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To address these challenges, this study designs a thermo\u2010responsive hydrogel (PNH) that encapsulates chitosan (CS)\u2010coated Fe\/Mn bimetallic nanozymes (FMCC) together with cholesterol oxidase (ChOx). FMCC displays multiple enzyme\u2010mimicking activities, including peroxidase (POD), catalase (CAT), and glutathione oxidase (GSHox). ChOx amplifies this catalytic cascade, enhancing reactive oxygen species (ROS) production and inducing ferroptosis\u2010mediated tumor cell death. The CS coating improves mucosal adhesion and tissue permeability, thereby facilitating intravesical delivery. Upon near\u2010infrared (NIR) irradiation, FMCC generates heat that liquefies the hydrogel, enabling spatiotemporally controlled drug release and providing mild photothermal therapy (MPTT). This photothermal effect acts synergistically with ferroptosis induction and immune modulation, concurrently minimizing damage to normal tissues. In parallel, ChOx disrupts cholesterol\u2010rich membrane rafts and promotes pro\u2010inflammatory M1 macrophage polarization. Released Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ions further potentiate immune activation by stimulating the cGAS\u2013STING pathway, driving IFN\u2010\u03b2 and IL\u20106 secretion, dendritic cell maturation, and T cell infiltration. Together, this nanozyme\u2013hydrogel system integrates tissue penetration, metabolic disruption, and immune stimulation, representing a promising strategy for localized bladder cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202513913","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T01:51:30Z","timestamp":1765590690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NIR\u2010Activatable Domino Cascade Catalysis Nanozyme Reactor for Multi\u2010Mechanism Synergistic Immunotherapy in Bladder Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Yongnan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology China\u2010Japan Union Hospital of Jilin University Changchun Jilin 130033 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Union Hospital of Jilin University Changchun Jilin 130033 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Cardiology China\u2010Japan Union Hospital of Jilin University Changchun Jilin 130033 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolic Dysregulation &amp; Prevention and Treatment of Esophageal Cancer Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical Sciences Zhengzhou University  Zhengzhou 450052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9718-337X","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology China\u2010Japan Union Hospital of Jilin University Changchun Jilin 130033 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