posted on 2021-01-08, 22:34authored byJian 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.