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However, it is still restricted by low ROS production efficiency and insufficient immune activation, due to intricate redox homeostasis in the tumor microenvironment (TME). Herein, a metalloprotein\u2010like hybrid nanozyme (FeS@GOx) is designed by in situ growth of nanozyme (ferrous sulfide, FeS) in a natural enzyme (glucose oxidase, GOx) to amplify ROS cascade for boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows the conversion of endogenous glucose to gluconic acid and hydrogen peroxide, which provides favorable increasing hydrogen peroxide for subsequent Fenton reaction of FeS nanozymes, thus reinforcing ROS production. Notably,\u00a0hydrogen sulfide (H<jats:sub>2<\/jats:sub>S)\u00a0release is activated by the gluconic acid generation\u2010related pH decrease, which can suppress the activity of endogenous thioredoxin reductase and catalase to further inhibit ROS elimination. Thus, FeS@GOx can sustainably amplify ROS accumulation and perturb intracellular redox homeostasis to improve chemodynamic therapy and trigger robust immunogenic cell death for effective immunotherapy combined with immune checkpoint blockade. This work proposes a feasible H<jats:sub>2<\/jats:sub>S amplified ROS cascade strategy employing a bioinspired hybrid nanozyme, providing a novel pathway to multi\u2010enzyme\u2010mediated TME modulation for precise and efficient chemodynamic immunotherapy.<\/jats:p>","DOI":"10.1002\/adhm.202300385","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T11:03:46Z","timestamp":1681211026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Wanying","family":"Sun","sequence":"first","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China) Collaborative Innovation Center for Guangxi Ethnic Medicine School of Chemistry and Pharmaceutical Sciences Guangxi Normal University  Guilin 541004 P. 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