A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy  

作　　者：Jie Sun Ziwen Zhang Hongyu Wu Xuemei Dong Chengjun Dong Lixin Sun Zhiqian Guo Yingchao Liu Xianfeng Gu Chunchang Zhao 

机构地区：[1]Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center,Institute of Fine Chemicals,School of Chemistry and Molecular Engineering,East China University of Science and Technology,Shanghai 200237,China [2]Department of Medicinal Chemistry,School of Pharmacy,Fudan University,Shanghai 201203,China [3]Shandong Provincial Hospital Affiliated to Shandong First Medical University,Shandong First Medical University&Shandong Academy of Medical Science,Jinan 250021,China

出　　处：《Science China Chemistry》2024年第7期2403-2411,共9页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(22077030,22271092,21977018,82173657);the Shanghai Municipal Science and Technology Major Project(2018SHZDZX03)。

摘　　要：Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

关 键 词：gas therapy precision gas release hydrogen sulfide depletion photodynamic therapy multimodal synergistic therapy 

分 类 号：TQ460.1[化学工程—制药化工] TB383.1[一般工业技术—材料科学与工程] R73-36[医药卫生—肿瘤]