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1篇 您的检索式:作者名="Stepan P.Chumakov"
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1Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors显示文摘Photodynamic therapy(PDT)is one of the most appealing photonic modalities for cancer treatment based on anticancer activity of light-induced photosensitizer-mediated reactive oxygen species(ROS),but a limited depth of light penetration into tissues does not make possible the treatment of deep-seated neoplasms and thus complicates its widespread clinical adoption.Here,we introduce the concept of genetically encoded bioluminescence resonance energy transfer(BRET)-activated PDT,which combines an internal light source and a photosensitizer(PS)in a single-genetic construct,which can be delivered to tumors seated at virtually unlimited depth and then triggered by the injection of a substrate to initiate their treatment.To illustrate the concept,we engineered genetic NanoLuc-miniSOG BRET pair,combining NanoLuc luciferase flashlight and phototoxic flavoprotein miniSOG,which generates ROS under luciferase-substrate injection.We prove the concept feasibility in mice bearing NanoLuc-miniSOG expressing tumor,followed by its elimination under the luciferase-substrate administration.Then,we demonstrate a targeted delivery of NanoLuc-miniSOG gene,via tumor-specific lentiviral particles,into a tumor,followed by its successful elimination,with tumor-growth inhibition(TGI)coefficient exceeding 67%,which confirms a great therapeutic potential of the proposed concept.In conclusion,this study provides proof-of-concept for deep-tissue“photodynamic”therapy without external light source that can be considered as an alternative for traditional PDT.Elena I.Shramova Stepan P.Chumakov Victoria O.Shipunova Anastasiya V.Ryabova Georgij B.Telegin Andrei V.Kabashin Sergey M.Deyev Galina M.Proshkina 2022Light(Science & Applications)2022,11,3:1
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