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GSH and H 2 O 2 Co‐Activatable Mitochondria‐Targeted Photodynamic Therapy under Normoxia and Hypoxia
Author(s) -
Sun Jian,
Du Ke,
Diao Jiajie,
Cai Xuetong,
Feng Fude,
Wang Shu
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202003895
Subject(s) - photosensitizer , photodynamic therapy , singlet oxygen , reactive oxygen species , chemistry , phototoxicity , superoxide , glutathione , photochemistry , hydrogen peroxide , tumor hypoxia , biophysics , oxygen , biochemistry , in vitro , biology , enzyme , medicine , organic chemistry , radiation therapy
Currently, photosensitizers (PSs) that are microenvironment responsive and hypoxia active are scarcely available and urgently desired for antitumor photodynamic therapy (PDT). Presented herein is the design of a redox stimuli activatable metal‐free photosensitizer (aPS), also functioning as a pre‐photosensitizer as it is converted to a PS by the mutual presence of glutathione (GSH) and hydrogen peroxide (H 2 O 2 ) 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, mito aPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H 2 O 2 . The mito aPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.