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Presented herein is the design of a redox stimuli activatable metal\u2010free photosensitizer (aPS), also functioning as a pre\u2010photosensitizer as it is converted to a PS by the mutual presence of glutathione (GSH) and hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) with high specificity on a basis of domino reactions on the benzothiadiazole ring. Superior to traditional PSs, the activated aPS contributed to efficient generation of reactive oxygen species including singlet oxygen and superoxide ion through both type 1 and type 2 pathways, alleviating the aerobic requirement for PDT. Equipped with a triphenylphosphine ligand for mitochondria targeting, <jats:sup><jats:bold>mito<\/jats:bold><\/jats:sup><jats:bold>aPS<\/jats:bold> showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. The <jats:sup><jats:bold>mito<\/jats:bold><\/jats:sup><jats:bold>aPS<\/jats:bold> was also compatible to near infrared PDT with two photon excitation (800\u2005nm) for extensive bioapplications.<\/jats:p>","DOI":"10.1002\/anie.202003895","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T05:04:25Z","timestamp":1587013465000},"page":"12122-12128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":213,"title":["GSH and H<sub>2<\/sub>O<sub>2<\/sub> Co\u2010Activatable Mitochondria\u2010Targeted Photodynamic Therapy under Normoxia and Hypoxia"],"prefix":"10.1002","volume":"59","author":[{"given":"Jian","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Polymer Science &amp; Engineering School of Chemistry and Chemical Engineering Nanjing University  Jiangsu Nanjing 210023 P. R. 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