Cascade Reactions by Nitric Oxide and Hydrogen Radical for Anti-Hypoxia Photodynamic Therapy Using an Activatable Photosensitizer

作者：Jian Sun, Xuetong Cai, Chengjun Wang, Ke Du, Weijian Chen, Fude Feng, Shu Wang · 发表于：Journal of the American Chemical Society · 年份：2021 · DOI：10.1021/jacs.0c10517 · 被引用次数：279 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Luminescence and Fluorescent Materials

Organelle-targeted activatable photosensitizers are attractive to improve the specificity and controllability of photodynamic therapy (PDT), however, they suffer from a big problem in the photoactivity under both normoxia and hypoxia due to the limited diversity of phototoxic species (mainly reactive oxygen species). Herein, by effectively photocaging a π-conjugated donor–acceptor (D–A) structure with an N-nitrosamine substituent, we established a unimolecular glutathione and light coactivatable photosensitizer, which achieved its high performance PDT effect by targeting mitochondria through both type I and type II (dual type) reactions as well as secondary radicals-participating reactions. Of peculiar interest, hydrogen radical (H • ) was detected by electron spin resonance technique. The generation pathway of H • via reduction of proton and its role in type I reaction were discussed. We demonstrated that the synergistic effect of multiple reactive species originated from tandem cascade reactions comprising reduction of O 2 by H • to form O 2 •– /HO 2 • and downstream reaction of O 2 •– with • NO to yield ONOO – . With a relatively large two-photon absorption cross section for photoexcitation in the near-infrared region (166 ± 22 GM at 800 nm) and fluorogenic property, the new photosensitizing system is very promising for broad biomedical applications, particularly low-light dose PDT, in both normoxic and hypoxic environments.