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Meanwhile, mild photothermal therapy (mPTT) enhances ferroptosis by accelerating lipid peroxidation. Herein, we designed a Janus nanoplatform that specifically arrests cells in thermo\u2010vulnerable S\u2010phase to maximize the ferroptosis\u2010sensitizing capacity of mPTT. A Janus architecture with a unique morphology was engineered to incorporate three functional modules: (1) A photothermal half\u2010bowl composed of polydopamine (PDA) that generates localized hyperthermia under near\u2010infrared (NIR) laser irradiation; (2) a drug\u2010loading module utilizing \u03c0\u2013\u03c0 stacking to deliver irinotecan (CPT\u201011), which arrests the cell cycle at the heat\u2010sensitive S\u2010phase and creates a favorable environment for mPTT; and (3) a ferroptosis\u2010inducing Fe\u2010zinc sulfide (ZnS) core anchored to the other half\u2010bowl, which initiates ferroptosis via Fe\n                    <jats:sup>2+<\/jats:sup>\n                    release and amplifies it through the ZnS component. This amplification operates via two mechanisms: hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S)\u2010mediated catalase (CAT) inhibition elevates H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    for the Fenton reaction, while Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010triggered p53 activation suppresses SLC7A11, disrupting the glutathione (GSH)\u2010glutathione peroxidase 4 (GPX4) antioxidant axis. The resulting nanoplatform demonstrated excellent antitumor efficacy, with ferroptosis confirmed as critical to its performance. This Janus nanoplatform presents a novel multi\u2010mechanism cooperative strategy for anticancer therapy centered on ferroptosis.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71437","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T08:40:01Z","timestamp":1783759201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Provoking Potent Cellular Ferroptosis in the Thermo\u2010Sensitive S\u2010Phase via CPT\u201011 Loaded Janus Nanomedicine for Enhanced Cancer Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Shiya","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy Harbin Medical University 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