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Reprogramming biothiol metabolism in tumor cells thus presents a promising strategy for enhancing anti\u2010tumor immunity. Here, we report the rational design of a densely accessible heteronuclear Fe\/Co dual\u2010atom nanozyme (FeCo DDA), which mimics natural flavoenzymes by coordinating high\u2010density Fe and Co active centers to regulate biothiol metabolism and induce intracellular disulfide accumulation. The dense heteronuclear diatomic catalytic center (with Fe and Co mass fractions of 10.35% and 11.32%, respectively) optimizes the Bader charge and d\u2010band center by adjusting electron redistribution, endowing it with excellent mimetic enzymatic activities for catalyzing the oxidation of biothiols to disrupt the homeostasis of tumor cells. Simultaneously, co\u2010loaded phlorizin inhibits glucose uptake, further driving compensatory cystine accumulation and disrupting glutathione biosynthesis. This dual action synergistically induces ferroptosis\u2010enhanced disulfidptosis, disrupting redox homeostasis and triggering immunogenic cell death. As a result, FeCo DDA co\u2010loaded with phlorizin (FeCo DDA\/P) not only enhances tumor cell immunogenicity but also reshapes the immunosuppressive tumor microenvironment, thereby potentiating anti\u2010tumor immune responses. This work highlights a dual\u2010atom nanozyme strategy to reprogram tumor metabolism and orchestrate multimodal cell death for effective tumor immunotherapy.<\/jats:p>","DOI":"10.1002\/anie.202524634","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T09:27:26Z","timestamp":1775467646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Charge\u2010Tunable Dense Dual\u2010Atom Nanozymes Reprogram Biothiol Metabolism Through Multi\u2010Enzyme\u2010Mimetic Catalysis to Synergistically Induce Ferroptosis and Disulfidptosis"],"prefix":"10.1002","volume":"65","author":[{"given":"Rui","family":"Niu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun  Jilin China"},{"name":"Department of Chemistry Tsinghua University  Beijing 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