Cascade Reactions by Nitric Oxide and Hydrogen Radical for Anti-Hypoxia Photodynamic Therapy Using an Activatable Photosensitizer
journal contributionposted on 2021-01-08, 22:34 authored by Jian Sun, Xuetong Cai, Chengjun Wang, Ke Du, Weijian Chen, Fude Feng, Shu Wang
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 O2 by H• to form O2•–/HO2• and downstream reaction of O2•– 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.
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Activatable Photosensitizer Organel...Anti-Hypoxia Photodynamic Therapycascade Reactionstandem cascade reactionsONOOphotosensitizing systemGMgeneration pathwayresonance techniquefluorogenic propertyHOunimolecular glutathionelight coactivatable photosensitizerreactive speciesreactive oxygen speciestype II800 nmO 2Nitric Oxidephototoxic speciesradicals-participating reactionsN-nitrosamine substituentphotodynamic therapyperformance PDT effectHydrogen Radicalhypoxic environmentstwo-photon absorptionlow-light dose PDT