Regulating Signal Pathway Triggers Circular Reactive Oxygen Species Production to Augment Oxidative Stress with Enzyme-Activated Nanoparticles

作     者：Benkai Bao Qiong Yuan Qian Feng Ling Li Meiqi Li Yanli Tang 

作者机构：Key Laboratory of Analytical Chemistry for Life Science of Shaanxi ProvinceKey Laboratory of Applied Surface and Colloid ChemistryMinistry of EducationSchool of Chemistry and Chemical EngineeringShaanxi Normal UniversityXi’anShaanxi Province 710119 

出 版 物：《CCS Chemistry》 (中国化学会会刊（英文）)

年 卷 期：2024年第6卷第3期

页      面：693-708页

核心收录：

学科分类：07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 

基　　金：supported by the National Natural Science Foundation of China(grant nos.22274095 and 21974084) the Innovation Capability Support Program of Shaanxi(program no.2021TD-42) the Fundamental Research Funds for the Central Universities(program nos.GK202302004,2021TS030,and GK202101001) 

主　　题：Keap1-Nrf2 pathway enzyme-activated probe reactive oxygen species oxidative stress antitumor therapy 

摘      要：Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very ***,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell *** OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and ***-SnMP@GE11 accumulated at tumor sites through specific targeting with ***-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ***,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative *** strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.