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Developing a stable and biocompatible molecular phototheranostic platform for TME\u2010activated second near\u2010infrared (NIR\u2010II) fluorescence imaging\u2010guided multimodal cascade therapy is a promising strategy for creating desirable anticancer agents. Herein, a new NIR\u2010II fluorescence imaging\u2010guided activatable molecular phototheranostic platform (IR\u2010FEP\u2010RGD\u2010S\u2010S\u2010S\u2010Fc) is presented for actively targeted tumor imaging and hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) gas\u2010enhanced chemodynamic\u2010hypothermal photothermal combined therapy (CDT\/HPTT). It is revealed for the first time that the coupling distance between IR\u2010FE and ferrocene is proportional to the photoinduced electron transfer (PET), and the aqueous environment is favorable for PET generation. The part of Cyclic\u2010RGDfK (cRGDfk) peptides can target the tumor and benefit the endocytosis of nanoparticles. The high\u2010concentration glutathione (GSH) in the TME will separate the fluorescence molecule and ferrocene by the GSH\u2010sensitive trisulfide bond, realizing light\u2010up NIR\u2010II fluorescence imaging and a cascade of trimodal synergistic CDT\/HPTT\/gas therapy (GT). In addition, the accumulation of hydroxyl radicals (\u2022OH) and down\u2010regulation of glutathione peroxidase 4 (GPX4) can produce excessive harmful lipid hydroperoxides, ultimately leading to ferroptosis.<\/jats:p>","DOI":"10.1002\/advs.202304104","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T16:29:53Z","timestamp":1700584193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Trisulfide Bond\u2010Mediated Molecular Phototheranostic Platform for \u201cActivatable\u201d NIR\u2010II Imaging\u2010Guided Enhanced Gas\/Chemo\u2010Hypothermal Photothermal Therapy"],"prefix":"10.1002","volume":"10","author":[{"given":"Gui\u2010long","family":"Wu","sequence":"first","affiliation":[{"name":"Center for Molecular Imaging Probe Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology Cancer Research Institute Hengyang Medical School University of South China  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