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The development of therapeutic gases that are tumor microenvironment responsive and efficiently reverse the TIME for precisely targeted tumor gas\u2010immunometabolic therapy remains a great challenge. In this study, a novel cancer cell membrane\u2010encapsulated pH\u2010responsive nitric oxide (NO)\u2010releasing biomimetic nanosystem (MP@AL) is prepared. Lactate oxidase (Lox) in MP@AL consumed oxygen to promote the decomposition of lactate, a metabolic by\u2010product of tumor glycolysis, and the generation of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, while L\u2010arginine (L\u2010Arg) in MP@AL is oxidized by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> to generate nitric oxide (NO). For one thing, NO led to mitochondrial dysfunction in tumor cells to reduce oxygen consumption and promote the efficiency of Lox in lactate decomposition, thus reversing lactate\u2010induced TIME; for another, NO effectively triggered immunogenic cell death, activated anti\u2010tumor immune response and long\u2010term immune memory, and ensured a favorable effect in the synergistic interaction with PD\u2010L1 antibody for inhibiting tumor growth and recurrence. Therefore, a novel gas\u2010immunometabolic therapy dual closed\u2010loop nanosystem for enhancing tumor immunogenicity and remodeling lactate\u2010induced TIME is established. Overall, this work will provide new ideas for gas therapy to effectively remodel the TIME to enhance cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/adma.202412655","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T03:12:40Z","timestamp":1731381160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Engineered Biomimetic Cancer Cell Membrane Nanosystems Trigger Gas\u2010Immunometabolic Therapy for Spinal\u2010Metastasized Tumors"],"prefix":"10.1002","volume":"37","author":[{"given":"Hongwei","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Zhongshan Hospital Fudan University  No.180 Fenglin Road Shanghai 200032 P. R. 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