Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic ef-ficacy and enhance anti-cancer outcomes.Here,we constructed doxorubicin(DOX)-loaded silk fibroin-based nanoparticles(NPs)with surface functionalization by photosensitizer(N770).The obtained na-notheranostics(N770-DOX@NPs)had desirable particle size(157 nm)and negative surface charge(-25 mV).These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli(acidic solution,reactive oxygen species,glutathione,and hyperthermia).Surface functionali-zation of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines,but not by normal cells.Furthermore,the intracellular NPs were found to be preferentially retained in mito-chondria,which were also efficient for near-infrared(NIR)fluorescence imaging,photothermal imaging,and photoacoustic imaging.Meanwhile,DOX could spontaneously accumulate in the nucleus.Impor-tantly,a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model,demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy(photothermal therapy and photodynamic therapy)and chemotherapy.Therefore,the present study brings new insight into the exploitation of an easy-to-use,versatile,and robust nanoplatform for programmable targeting,imaging,and applying synergistic therapy to tumors.

Shuangquan Gou;Nanxi Chen;Xiaoai Wu;Menghang Zu;Shixiong Yi;Binwu Ying;Fangyin Dai;Bowen Ke;Bo Xiao

Laboratory of Anesthesiology & Critical Care Medicine,Department of Anesthesiology,West China Hospital,Sichuan University,Chengdu 610041,China;State Key Laboratory of Silkworm Genome Biology,College of Sericulture,Textile and Biomass Sciences,Southwest University,Chongqing 400715,China;Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing,School of Materials and Energy,Southwest University,Chongqing 400715,China;Department of Nuclear Medicine,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu 610041,China

药学学报（英文版）

[1]Shuangquan Gou;Nanxi Chen;Xiaoai Wu;Menghang Zu;Shixiong Yi;Binwu Ying;Fangyin Dai;Bowen Ke;Bo Xiao-.Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy)[J].药学学报（英文版）,2022(01):406-423

N770,notheranostics,functionali,chondria

Multi,responsive,nanotheranostics,enhanced,penetration,oxygen,self,producing,capacities,multimodal,synergistic,Incorporation,multiple,functions,into,nanoplatform,improve,diagnostic,ficacy,anti,outcomes,Here,constructed,doxorubicin,DOX,loaded,silk,fibroin,nanoparticles,NPs,surface,functionalization,by,photosensitizer,obtained,had,desirable,size,negative,charge,mV,These,presented,excellent,generating,capacity,responded,quadruple,stimuli,acidic,solution,reactive,species,glutathione,hyperthermia,Surface,could,endow,them,internalization,cancerous,lines,but,normal,cells,Furthermore,intracellular,were,found,preferentially,retained,which,also,efficient,near,infrared,NIR,fluorescence,imaging,photothermal,photoacoustic,Meanwhile,spontaneously,accumulate,nucleus,Impor,tantly,mouse,test,treated,plus,irradiation,achieved,best,retardation,among,treatment,groups,bearing,models,patient,derived,xenograft,demonstrating,unprecedented,therapeutic,effects,trimodal,guided,mitochondrial,phototherapy,photodynamic,chemotherapy,Therefore,study,brings,new,insight,exploitation,easy,versatile,robust,programmable,targeting,applying,tumors

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