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Here, an iridium (Ir)\u2010based nanozyme (IIN) was constructed through coordination\u2010driven co\u2010assembly using photosensitizer indocyanine green (ICG), Ir, and indoleamine 2,3\u2010dioxygenase (IDO) inhibitor NLG8189. Then, the IIN was mimicked by tumor cell lysate (TCL)\u2010simulated dendritic cell (DC) membrane to form IIN@M. Based on superior enzyme\u2010like activity and photothermal performance, IIN@M disrupted the intracellular redox homeostasis by generating reactive oxygen species (ROS) and depleting glutathione (GSH). GSH depletion induced ferroptosis, and ROS burst under photothermal irradiation triggered pyroptosis, thus synergistically enhancing immunogenic cell death (ICD). The generated ROS could promote mitochondrial DNA (mtDNA) oxidative damage and release, finally activating the immune response by the cyclic GMP\u2010AMP synthase\u2010simulator of interferon gene (cGAS\u2010STING) pathway. In vivo experiments also suggested that IIN@M could efficiently ablate the primary tumor, especially under photothermal irradiation. Furthermore, it could suppress distant tumor progression by triggering the immune response, especially under photothermal irradiation, which was accompanied by increased DC maturation, M1 macrophage polarization, and T cell infiltration in tumor tissue. This study proposed a promising strategy for effective Ir\u2010based nanozyme in tumor immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.202519186","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:02:21Z","timestamp":1768910541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biomimetic Iridium\u2010Based Photothermal Nanozyme to Trigger Ferroptosis and Pyroptosis and Activate the cGAS\u2010STING Pathway for Improved Tumor Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Lijun","family":"Ding","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-9530","authenticated-orcid":false,"given":"Zhongxiong","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukai","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longlong","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Institute of Materia Medica Xinjiang University  Urumqi China"},{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3295-6096","authenticated-orcid":false,"given":"Jinyao","family":"Li","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Biological Resources and Genetic Engineering College of Life Science and Technology Xinjiang University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_9_2_1","article-title":"Endogenous\/Exogenous Dual\u2010responsive Nanozyme for Photothermally Enhanced Ferroptosis\u2010immune Reciprocal Synergistic Tumor Therapy","volume":"11","author":"Zhang H. 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