Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment.In this study,a novel redox-responsive polymeric prodrug(molecular weight,MW:93.5 kDa)was produced by reversible addition-fragmentation chain transfer(RAFT)polymeriza-tion.The amphiphilic block polymer-doxorubicin(DOX)prodrug was employed to deliver a hydrophobic photosensitizer(PS),chlorin e6(Ce6),and the as-prepared nanoscale system[NPs(Ce6)]was investigated as a chemo-photodynamic anti-cancer agent.The glutathione(GSH)-cleavable disulfide bond was in-serted into the backbone of the polymer for biodegradation inside tumor cells,and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly.NPs(Ce6)released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH.NPs(Ce6)showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells,which was confirmed from a collapsed cell morphology,a lifted level in the intracel-lular reactive oxygen species,a reduced viability and induced apoptosis.Moreover,ex vivo fluorescence images indicated that NPs(Ce6)retained in the tumor,and exhibited a remarkable in vivo anticancer ef-ficacy.The combinational therapy showed a significantly increased tumor growth inhibition(TGI,58.53％).Therefore,the redox-responsive,amphiphilic block polymeric prodrug could have a great po-tential as a chemo-photodynamic anti-cancer agent.

Lei Luo;Yiming Qi;Hong Zhong;Shinan Jiang;Hu Zhang;Hao Cai;Yahui Wu;Zhongwei Gu;Qiyong Gong;Kui Luo

College of Pharmaceutical Sciences,Southwest University,Chongqing 400716,China;Amgen Bioprocessing Centre,Keck Graduate Institute,Claremont,CA 91711,USA;Huaxi MR Research Center(HMRRC),Department of Radiology,Functional and Molecular Imaging Key Laboratory of Sichuan Province,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China;Research Unit of Psychoradiology,Chinese Academy of Medical Sciences,Chengdu 610041,China

药学学报（英文版）

[1]Lei Luo;Yiming Qi;Hong Zhong;Shinan Jiang;Hu Zhang;Hao Cai;Yahui Wu;Zhongwei Gu;Qiyong Gong;Kui Luo-.GSH-sensitive polymeric prodrug:Synthesis and loading with photosensitizers as nanoscale chemo-photodynamic anti-cancer nanomedicine)[J].药学学报（英文版）,2022(01):424-436

polymeriza

GSH,sensitive,polymeric,prodrug,Synthesis,loading,photosensitizers,nanoscale,chemo,photodynamic,nanomedicine,Precisely,delivering,combinational,therapeutic,agents,has,become,crucial,challenge,tumor,treatment,In,this,study,novel,redox,responsive,molecular,weight,kDa,was,produced,by,reversible,addition,fragmentation,chain,transfer,RAFT,amphiphilic,block,doxorubicin,DOX,employed,hydrophobic,PS,chlorin,Ce6,prepared,system,NPs,investigated,glutathione,cleavable,disulfide,bond,serted,into,backbone,biodegradation,inside,cells,conjugated,onto,successfully,released,intracellularly,their,original,structures,degraded,segments,low,MWs,presence,showed,effect,kill,4T1,murine,breast,which,confirmed,from,collapsed,morphology,lifted,level,reactive,oxygen,species,reduced,viability,induced,apoptosis,Moreover,vivo,fluorescence,images,indicated,that,retained,exhibited,remarkable,anticancer,ficacy,therapy,significantly,increased,growth,inhibition,TGI,Therefore,could,have,great,tential

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