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

作     者：Xuan Xiao Qingyu Zong Jisi Li Youyong Yuan 

作者机构：School of Biomedical Sciences and EngineeringSouth China University of TechnologyGuangzhou 511442 National Engineering Research Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510006 School of MedicineSouth China University of TechnologyGuangzhou 510006 Key Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006 Guangdong Provincial Key Laboratory of Biomedical EngineeringSouth China University of TechnologyGuangzhou 510006 

出 版 物：《CCS Chemistry》 (中国化学会会刊（英文）)

年 卷 期：2022年第4卷第12期

页      面：3878-3888页

学科分类：1002[医学-临床医学] 0703[理学-化学] 100214[医学-肿瘤学] 10[医学] 

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 

主　　题：prodrug cascade drug activation oxidation-chemotherapy cancer therapy drug delivery 

摘      要：Efficacy of prodrugs in cancer therapy requires selective and efficient drug activation in cancer ***,we report a novel dual-prodrug delivery system with tumor-selective cascade-amplified prodrug activation for synergistic *** 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 ***,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 *** findings provide new insights to inform precise cooperative cancer therapy.