Abstract
Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals(·OH)in the tumor mi-croenvironment(TME)for chemodynamic therapy(CDT)with high specificity.However,the low pH en-vironment and insufficient endogenous hydrogen peroxide(H2O2)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 H2O2 by ascorbate to produce more toxic·OH to trigger the apop-tosis 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 H2O2 significantly enhanced the synergistic effect of CDT by oxidative damage.To-gether 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.
基金项目
National Key Research and Development Program of China(2019YFA0705803)
National Natural Science Foundation of China Youth Fund(51803174)
National Natural Science Foundation of China Youth Fund(82102470)
Natural Science Foundation of Sichuan Province(24NSFSC4798)
Foundation of Sichuan Engineering Technology Research Center of Basalt Fiber Composites Development and Application of South(2022SCXWYXWFC002)
维普
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