典型文献
Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors
文献摘要：
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.
文献关键词：
中图分类号：
作者姓名：
Elena I.Shramova;Stepan P.Chumakov;Victoria O.Shipunova;Anastasiya V.Ryabova;Georgij B.Telegin;Andrei V.Kabashin;Sergey M.Deyev;Galina M.Proshkina
作者机构：
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry,Russian Academy of Sciences,16/10 Miklukho-Maklaya Street,Moscow 117997,Russia;MEPhI(Moscow Engineering Physics Institute),Institute of Engineering Physics for Biomedicine(PhysBio),31 Kashirskoe shosse,Moscow 115409,Russia;Prokhorov General Physics Institute,Russian Academy of Sciences,Vavilova,38,Moscow 119991,Russia;Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry,Russian Academy of Sciences,Prospect Nauki 6,Pushchino 142290,Russia;Aix Marseille University,CNRS,LP3,163 Ave.De Luminy,Case 917,13288 Marseille,France
文献出处：
引用格式：
[1]Elena I.Shramova;Stepan P.Chumakov;Victoria O.Shipunova;Anastasiya V.Ryabova;Georgij B.Telegin;Andrei V.Kabashin;Sergey M.Deyev;Galina M.Proshkina-.Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors)[J].光：科学与应用（英文版）,2022(03):311-323
A类：
miniSOG,flashlight,phototoxic
B类：
Genetically,encoded,BRET,activated,photodynamic,therapy,treatment,deep,seated,tumors,Photodynamic,PDT,one,most,appealing,photonic,modalities,anticancer,activity,induced,photosensitizer,mediated,reactive,oxygen,species,ROS,but,depth,penetration,into,tissues,does,not,make,possible,neoplasms,thus,complicates,its,widespread,clinical,adoption,Here,introduce,concept,genetically,bioluminescence,resonance,energy,transfer,which,combines,internal,source,PS,single,construct,delivered,virtually,unlimited,then,triggered,by,injection,substrate,initiate,their,To,illustrate,engineered,NanoLuc,pair,combining,luciferase,flavoprotein,generates,under,We,prove,feasibility,mice,bearing,expressing,followed,elimination,administration,Then,demonstrate,targeted,delivery,via,specific,lentiviral,particles,successful,growth,inhibition,TGI,coefficient,exceeding,confirms,great,therapeutic,potential,proposed,In,conclusion,this,study,provides,proof,without,external,that,considered,alternative,traditional
AB值：
0.562376
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