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.
Currently,p hotosensitizers (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 ar edox stimuli activatable metal-free photosensitizer (aPS), also functioning as ap re-photosensitizer as it is converted to aP S by the mutual presence of glutathione (GSH) and hydrogen peroxide(H 2 O 2)w ith high specificity on ab asis of domino reactions on the benzothiadiazolering. Superior to traditional PSs,t he activated aPS contributed to efficient generation of reactive oxygen species including singlet oxygen and superoxide ion through both type 1and type 2pathways,alleviating the aerobic requirement for PDT.E quipped with at riphenylphosphine ligand for mitochondria targeting, mito aPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions,a fter activation by intracellular GSH and H 2 O 2 .T he mito aPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.
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 (H2O2) 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, mitoaPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H2O2. The mitoaPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.
Environment-responsive in situ synthesis of molecular fluorescent dyes is challenging. Herein, we develop a photoextension strategy to make trimethine cyanines with decent conversion efficiency (up to 81 %) using 1-butyl 2,3,3-trimethyl 3H-indole derivatives as the sole precursors, and demonstrate a free radical mechanism. In the inducer-extension stage, free radicals and reactive oxygen species (ROS) were able to mediate similar reactions with no assistance of light. We explored a Mito-extension strategy to in situ synthesize trimethine cyanines in the living cells. The cellular ROS-dependence provided a foundation for preferential cyanine expression in cancer cells. Finally, we applied an iodized precursor as an intrinsic ROS-activated theranostic agent that integrated mitochondria-targeted cyanine synthesis, cell imaging and phototherapy.
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