pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy  

作　　者：Jianhua Zou Zheng Li Yang Zhu Yucen Tao Qing You Fangfang Cao Qinghe Wu Min Wu Junjie Cheng Jianwei Zhu Xiaoyuan Chen 

机构地区：[1]Departments of Diagnostic Radiology,Surgery,Chemical and Biomolecular Engineering,and Biomedical Engineering,Yong Loo Lin School of Medicine and College of Design and Engineering,National University of Singapore,Singapore,119074,Singapore [2]Nanomedicine Translational Research Program,NUS Center for Nanomedicine,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,117597,Singapore [3]Clinical Imaging Research Centre,Centre for Translational Medicine,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,117599,Singapore [4]Institute of Molecular and Cell Biology,Agency for Science,Technology,and Research(A*STAR),61 Biopolis Drive,Proteos,Singapore,138673,Singapore [5]Department of Plastic and Reconstructive Surgery,Shanghai Ninth People’s Hospital,Shanghai Jiaotong University,Shanghai,200011,PR China [6]Department of Chemistry Center for Bioanalytical Chemistry,University of Science and Technology of China,Hefei,230026,PR China [7]College of Life Science,Nanjing Normal University,1 Wenyuan Road,Nanjing,210023,PR China

出　　处：《Bioactive Materials》2024年第4期414-421,共8页生物活性材料（英文）

基　　金：the National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine);National Medical Research Council(MOH-001388-00,MOH-001041,CG21APR1005);Singapore Ministry of Education(MOE-000387-00);National Research Foundation(NRF-000352-00);the Open Fund Young Individual Research Grant of Singapore(MOH-001127-01).

摘　　要：Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy(PDT)due to oxygen consumption.Type I PDT,which can operate independently of oxygen,is a viable option for treating hypoxic tumors.In this study,we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment(TME)to enhance type I PDT through glutathione(GSH)depletion.Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals(O_(2)^(-).)while minimizing their consumption.The diisopropyl group within PEG-IR820 serves a dual purpose:it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820,facilitating efficient O_(2)^(-).generation.Simultaneously,the release of JSK leads to GSH depletion,resulting in the generation of nitric oxide(NO).This,in turn,contributes to the formation of highly cytotoxic peroxynitrite(ONOO^(-).),thereby enhancing the therapeutic efficacy of these NPs.NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

关 键 词：TME responsive NO gas therapy NIR-II imaging Type I PDT 

分 类 号：R318[医药卫生—生物医学工程]