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Herein, we report a glutathione (GSH)\u2010responsive multifunctional nanodrug FeCe6@SKN that is self\u2010assembled from the complex formed by the coordination of the photosensitizer Ce6, the natural anticancer agent Shikonin (SKN), and ferric ions (Fe\n                    <jats:sup>3+<\/jats:sup>\n                    ). After tail vein injection, FeCe6@SKN can effectively accumulate at the tumor site through the EPR effect and subsequently disassemble by high concentration of GSH, leading to the controlled release of Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , Ce6, and SKN. This GSH\u2010triggered disassembly and resulting size reduction not only improve the tissue penetration ability of nanodrugs but also enhance the fluorescence signals as well as the singlet oxygen generation capacity of Ce6, enabling efficient photodynamic therapy (PDT). Shikonin simultaneously triggers cancer cell apoptosis by upregulating the pro\u2010apoptotic protein Bax and downregulating the antiapoptotic protein Bcl\u20102. More notably, the excessive accumulation of intracellular iron ions induces ferroptosis and further suppress tumor growth. It is evidently demonstrated that this multimodal therapeutic approach that combines ferroptosis, PDT, and chemotherapy significantly reduces the drug dosage and improves the therapeutic efficacy. This work may provide a universal and promising approach for developing intelligent and tumor microenvironment\u2010responsive nanodrugs for effective cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505738","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:16:02Z","timestamp":1774340162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutathione\u2010Triggered Nanodrug Disassembly for Enhanced Combined Ferroptosis and Photodynamic\u2010Chemotherapy of Tumors"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0386-6625","authenticated-orcid":false,"given":"Anna","family":"Wang","sequence":"first","affiliation":[{"name":"School of Biological and Chemical Engineering Zhejiang University of Science and Technology  Hangzhou 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Protection School of Radiation Medicine and Protection Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou 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