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Inspired by the natural mechanism of a radical storm in inflammatory cells via activated and regulatable biocatalysis, the authors herein report a self\u2010powered nanozyme that can enable RONS production in tumor cells via cascade reactions. The nanozymes are constructed via glucose oxidase (GOx)\u2010templated inverse microemulsion polymerization from acrylamide, arginine\u2010acrylamide, ferrocene\u2010acrylate, and <jats:italic>N,N\u2032<\/jats:italic>\u2010bis(acryloyl)cystamine, followed by surface coating with hyaluronic acid. After targeted delivery into cancer cells, the nanozymes are dissociated by intracellular glutathione\u00a0to release GOx, which decomposed glucose to generate gluconic acid and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Under such acidified conditions, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> efficiently oxidized pendant arginine residues to produce nitric oxide , transformed into a highly toxic hydroxyl radical and superoxide anion via ferrocene\u2010mediated Fenton reaction and Haber\u2013Weiss cycle, and simultaneously generated peroxynitrite anion via reaction between NO and \u00b7O<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>, thus provoking the RONS radical storm to effectively eradicate A549 tumor cells both in vitro and in vivo. This nature\u2010inspired enzyme\u2010chemical dynamic therapy may provide a promising modality for anti\u2010cancer treatment.<\/jats:p>","DOI":"10.1002\/smtd.202201641","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T06:42:19Z","timestamp":1673073739000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inflammatory Cell\u2010Inspired Cascade Nanozyme Induces Intracellular Radical Storm for Enhanced Anticancer Therapy"],"prefix":"10.1002","volume":"7","author":[{"given":"Xun","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Functional Nano and Soft Materials (FUNSOM) Jiangsu Key Laboratory of Carbon\u2010Based Functional Materials and Devices Soochow University  Suzhou 215123 P. R. China"},{"name":"Department of Thoracic Surgery The Second Affiliated Hospital of Soochow University  Suzhou 215004 P. R. 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