Cerenkov radiation induced chemo-photodynamic therapy using ROS-responsive agent
Traditional photodynamic therapy (PDT) suffers from poor tissue penetration due to using external light as excitation source. Cerenkov radiation (CR) from radionuclides can serve as an internal light source to activate photosensitizers inside lesion tissues. Using CR instead of external light in PDT is thought to be an effective way to overcome the shortcoming of traditional PDT. However, the weakness of CR emission limits the outcomes of CR-induced PDT (CR-PDT). We anticipated that CR-induced combined therapy could effectively enhance the therapeutic outcome of CR-PDT. Herein, a ROS-responsive Chemo-PDT agent ( TTC ) was synthesized by conjugation of tetraphenylporphyrin (photosensitizer) with camptothecin (chemotherapeutic drug) through a ROS-cleavable thioketal linker. Under activation by CR emission from gallium-68 ( 68 Ga), the porphyrin moiety could generate ROS , which then cleaves the thioketal linker to induce the subsequent release of CPT. Using [ 68 Ga]Ga-NOTA-Nb109 as an intracellular CR emitter, in comparison with its non-cleavable analogue ( TUC ) only displaying phototoxicity, TTC exhibited much higher cytotoxicity toward A375-hPD-L1 cells due to its combined effect of PDT and chemotherapy. Our work presents a new strategy to use ROS-responsive Chemo-PDT agent to improve the outcomes of CR-PDT.
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