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To address this, we developed an innovative bimetallic nanozyme, Fe\/Zn-CNZ@LOx@PEG, that integrates catalytic activity with metabolic and immune modulation. This nanoplatform executes a novel \u201cmetabolic-immuno\u201d co-regulation strategy. Its Fe\u2013Zn catalytic sites drive a lactate-fueled cascade reaction within the acidic tumor milieu, generating a burst of cytotoxic hydroxyl radicals. Simultaneously, released zinc ions rectify tumor zinc deficiency, disrupting cellular metabolism and promoting ferroptosis\u2014an iron-dependent cell death\u2014through glutathione depletion and lipid peroxidation. This ferroptotic cell death, in turn, acts as a potent trigger for immunogenic cell death (ICD), stimulating dendritic cell maturation and cytotoxic T cell infiltration to reverse immunosuppression. Consequently, Fe\/Zn-CNZ@LOx@PEG demonstrates potent tumor suppression and effectively enhances the efficacy of anti-PD-1 therapy in a prostate cancer mouse model. This work presents a catalytic nanoreactor that co-regulates metabolism and immunity, offering a robust and synergistic strategy for the ferroptosis-immunotherapy of advanced cancers.<\/jats:p>","DOI":"10.34133\/bmr.0378","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T16:55:41Z","timestamp":1780419341000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Restoring Zinc Homeostasis via a Bimetallic Nanozyme to Amplify Ferroptosis and Antitumor Immunity for Prostate Cancer Treatment"],"prefix":"10.34133","volume":"30","author":[{"given":"Jinzhuo","family":"Ning","sequence":"first","affiliation":[{"name":"Department of Urology, \rRenmin Hospital of Wuhan University, Wuhan430060, Hubei Province, P.R. 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