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 insuffic...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.展开更多
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)+4 种基金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 UniversitySichuan International Science and Technology Cooperation BaseDalian Institute of Chemical Physics of Chinese Academy of Sciences。
文摘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.
