Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy  

作　　者：Xuan Xiao Qingyu Zong Jisi Li Youyong Yuan 

机构地区：[1]School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou 511442 [2]National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006 [3]School of Medicine,South China University of Technology,Guangzhou 510006 [4]Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,South China University of Technology,Guangzhou 510006 [5]Guangdong Provincial Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006

出　　处：《CCS Chemistry》2022年第12期3878-3888,共11页中国化学会会刊（英文）

基　　金：This work was supported by the National Natural Science Foundation of China(nos.52073101 and 51873072);the Science and Technology Program of Guangzhou(no.202102010025);Guangdong Provincial Pearl River Talents Program(no.2019QN01Y088);the Special Fund for the Construction of High-level Key Clinical Specialty(Medical Imaging)in Guangzhou,Guangzhou Key Laboratory of Molecular Imaging and Clinical Translational Medicine.

摘　　要：Efficacy of prodrugs in cancer therapy requires selective and efficient drug activation in cancer cells.Here,we report a novel dual-prodrug delivery system with tumor-selective cascade-amplified prodrug activation for synergistic oxidation-chemotherapy.Cancer cells overexpressing cathepsin B-activatable nearinfrared(NIR)hemicyanine prodrug(CyNH-Citval)were encapsulated by the reactive oxygen species(ROS)-responsive polyprodrug of doxorubicin(DOX)(PTK_(DOX))to obtain PTK_(DOX/Cy).Upon uptake of PTK_(DOX/Cy) by cancer cells and subsequent prodrug CyNH-Citval activation,NIR fluorescence was turned on and toxicity toward mitochondria was restored,thereby elevating intracellular ROS levels,which subsequently activated the polyprodrug PTK_(DOX) to initiate the cascade and amplify DOX.Overall,these results indicate that enzyme-mediated initiation of drug activation and amplification of cascade ROS ultimately causes selective and efficient prodrug activation in tumors with synergistic oxidation and chemotherapy.These findings provide new insights to inform precise cooperative cancer therapy.

关 键 词：PRODRUG cascade drug activation oxidation-chemotherapy cancer therapy drug delivery 

分 类 号：R730.53[医药卫生—肿瘤]