Active-transporting of charge-reversal Cu(Ⅱ)-doped mesoporous silica nanoagents for antitumor chemo/chemodynamic therapy  

作　　者：Zhaomin Tang Qian He Jianren Zhou Shuang Yan Li Jiang Yudong Wang Chenxing Yao Huangzhao Wei Keda Yang Jiajia Wang 

机构地区：[1]School of New Energy and Materials,Southwest Petroleum University,Chengdu 610500,China [2]Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,China [3]Shulan International Medical College,Zhejiang Shuren University,Hangzhou 310015,China [4]Department of Laboratory Medicine,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu 610072,China

出　　处：《Chinese Chemical Letters》2024年第7期400-406,共7页中国化学快报（英文版）

基　　金：financially supported by the National Key Research and Development Program of China(No.2019YFA0705803);the National Natural Science Foundation of China Youth Fund(Nos.51803174,82102470);the Natural Science Foundation of Sichuan Province(No.24NSFSC4798);the Foundation of Sichuan Engineering Technology Research Center of Basalt Fiber Composites Development and Application of Southwest Petroleum University(No.2022SCXWYXWFC002);the support from the School of New Energy and Materials of Southwest Petroleum University;Sichuan International Science and Technology Cooperation Base;Dalian Institute of Chemical Physics of Chinese Academy of Sciences。

摘　　要：Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals(·OH)in the tumor microenvironment(TME)for chemodynamic therapy(CDT)with high specificity.However,the low pH environment and insufficient endogenous hydrogen peroxide(H_(2)O_(2))of the highly efficient Fenton reaction limits its practical application in clinic.Here,a Cu(Ⅱ)-doped mesoporous silica nanoagent(Cu-MSN)with excellent dispersity was successfully developed.After loaded with doxorubicin(DOX)and ascorbate(AA),Cu-MSN@DA was coated with active targeting ligand folic acid(FA),dimethyl maleic an-hydride(DMMA)and carboxymethyl chitosan(CMC)to obtain an active transporting nanoagent(FCDC@Cu-MSN@DA)with tunable charge-reversal property,which is more adaptable to the pH value of TME than Fe-based Fenton agents,and can self-supply exogenous H_(2)O_(2)by ascorbate to produce more toxic·OH to trigger the apoptosis of cancer cells.Meanwhile,the high level of glutathione(GSH)in TME can reduce Cu(Ⅱ)to Cu(I)by Fenton-like reaction,increasing the generation rate of·OH and relieving tumor antioxidant ability.The supply of exogenous H_(2)O_(2)significantly enhanced the synergistic effect of CDT by oxidative damage.Together with DOX-induced cell apoptosis,this novel nanoagent FCDC@Cu-MSN@DA can achieve maximum therapeutic efficacy,creating a new model of safe and effective tumor treatment with high specificity.

关 键 词：Cu(Ⅱ)-doped ASCORBATE Hydrogen peroxide Charge-reversal Oxidative damage 

分 类 号：TB383.1[一般工业技术—材料科学与工程] TQ460.1[化学工程—制药化工]