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Nanozyme\u2010based antitumor catalysis is associated with precise immune activation in the tumor microenvironment (TME). In this study, a cascade\u2010augmented nanoimmunomodulator (CMZM) with multienzyme\u2010like activities, which includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), that dissociates under an acidic and abundant GSH TME, is proposed for multimodal imaging\u2010guided chemodynamic therapy (CDT)\/photodynamic therapy (PDT) enhanced immunotherapy. Vigorous multienzyme\u2010like activities can not only produce O<jats:sub>2<\/jats:sub> to alleviate hypoxia and promote the polarization of M2 to M1 macrophages, but also generate ROS (\u2022OH and <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>) and deplete GSH in the TME to expose necrotic cell fragments and reverse immunosuppressive TME by eliciting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes (CTLs) in tumors. Therefore, inhibitory effects on both primary and distant tumors are achieved through synergy with an \u03b1\u2010PD\u2010L1 blocking antibody. This cascade multienzyme\u2010based nanoplatform provides a smart strategy for highly efficient ICB immunotherapy against \u201ccold\u201d tumors by revising immunosuppressive TME.<\/jats:p>","DOI":"10.1002\/adma.202306748","type":"journal-article","created":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:54:30Z","timestamp":1694325270000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Augmenting Immunotherapy via Bioinspired MOF\u2010Based ROS Homeostasis Disruptor with Nanozyme\u2010Cascade Reaction"],"prefix":"10.1002","volume":"35","author":[{"given":"Ruifang","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in Wuhan Wuhan Institute of Physics and Mathematics Innovation Academy for Precision Measurement Science and Technology Chinese Academy of Sciences\u2010Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology  Wuhan 430071 P. 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