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Herein, a strategy of Fenton reaction cycloacceleration initiated by remodeling the TME for magnetic resonance imaging (MRI)\u2010guided high\u2010performance ferroptosis therapy of tumors is proposed. The synthesized nanocomplex exhibits enhanced accumulation at carbonic anhydrase IX (CAIX)\u2010positive tumors based on the CAIX\u2010mediated active targeting, and increased acidification via the inhibition of CAIX by 4\u2010(2\u2010aminoethyl) benzene sulfonamide (ABS) (remodeling TME). This accumulated H<jats:sup>+<\/jats:sup> and abundant glutathione in TME synergistically trigger biodegradation of the nanocomplex to release the loaded cuprous oxide nanodots (CON), <jats:italic>\u03b2<\/jats:italic>\u2010lapachon (LAP), Fe<jats:sup>3+<\/jats:sup>, and gallic acid\u2010ferric ions coordination networks (GF). The Fenton and Fenton\u2010like reactions are cycloaccelerated via the catalytic loop of Fe\u2010Cu, and the LAP\u2010triggered and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase1\u2010mediated redox cycle, generating robust ROS and plenitudinous lipid peroxides accumulation for ferroptosis of tumor cells. The detached GF network has improved relaxivities in response to the TME. Therefore, the strategy of Fenton reaction cycloacceleration initiated by remodeling the TME is promising for MRI\u2010guided high\u2010performance ferroptosis therapy of tumors.<\/jats:p>","DOI":"10.1002\/adhm.202203362","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T18:44:50Z","timestamp":1678387490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["A Strategy of Fenton Reaction Cycloacceleration for High\u2010Performance Ferroptosis Therapy Initiated by Tumor Microenvironment Remodeling"],"prefix":"10.1002","volume":"12","author":[{"given":"Lin","family":"Huang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Southern Medical University  1023 Shatai South Road Guangzhou Guangdong 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[{"name":"Medical Imaging 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