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However, the inherent selectivity of CDT will be affected after introducing peroxide\u2010supplementing functionality into chemodynamic agents due to the lack of ability to distinguish cancer cells from normal cells. Here, an intelligent CDT nanomedicine is reported with both cascade\u2010responsive and peroxide self\u2010supplying performances for specific and efficient cancer treatment. Upon endocytosis into acidic endo\/lysosomes, the CDT nanomedicine comprising methyl linoleate hydroperoxide (MLH)\u2010loaded amorphous iron oxide nanoparticles (AIO@MLH NPs) can be decomposed to release MLH and Fe<jats:sup>3+<\/jats:sup> that is further reduced into Fe<jats:sup>2+<\/jats:sup> by endo\/lysosomal six\u2010transmembrane epithelial antigen of the prostate (STEAP) with metalloreductase activity, enabling the occurrence of Fenton\u2010type reaction between high\u2010active Fe<jats:sup>2+<\/jats:sup> and MLH for free radical generation, which causes endo\/lysosomal damage and cancer cell apoptosis. Noteworthily, AIO@MLH NPs exhibit potent chemodynamic cytotoxicity to cancerous cells rather than non\u2010cancerous cells benefiting from the overexpressed STEAP in multiple cancers, thereby leading to precise tumor CDT. This work highlights the use of endogenous STEAP to improve the selectivity of peroxide self\u2010supplying chemodynamic agents and paves the way for the development of precision medicine.<\/jats:p>","DOI":"10.1002\/adhm.202500752","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T06:12:23Z","timestamp":1745993543000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A pH\/STEAP Cascade\u2010Responsive Nanomedicine with Self\u2010Supplied Peroxide for Precise Chemodynamic Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Huilan","family":"Cai","sequence":"first","affiliation":[{"name":"New Cornerstone Science Laboratory MOE Key Laboratory for Analytical Science of Food Safety and Biology College of Chemistry Fuzhou University  Fuzhou 350108 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