Intelligent nanoreactor coupling tumor microenvironment manipulation and H_(2)O_(2)-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors  

作　　者：Jie Liu Tianfeng Yang Handan Zhang Lin Weng Xiuhong Peng Tao Liu Cheng Cheng Yanmin Zhang Xin Chen 

机构地区：[1]School of Chemical Engineering and Technology,Shaanxi Key Laboratory of Energy Chemical Process Intensification,Institute of Polymer Science in Chemical Engineering,Xi’an Jiaotong University,Xi’an,710049,China [2]School of Pharmacy,Health Science Center,Xi’an Jiaotong University,Xi’an,710061,China [3]National&Local Joint Engineering Research Center of Biodiagnosis and Biotherapy,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an,710004,China

出　　处：《Bioactive Materials》2024年第4期354-365,共12页生物活性材料（英文）

基　　金：supported by the National High Level Talents Special Support Plan(X.C.);the National Natural Science Foundation of China(82272141 to X.C.);the“Young Talent Support Plan”of Xi’an Jiaotong University(X.C.);the Shaanxi Innovative Research Team of Science and Technology(S2023-ZC-TD-0152);the Natural Science Foundation of Shaanxi Province(2022JZ-48 to X.C.);the National Key Research and Development Program of China(2023YFC2509104 to X.C.);the Postdoctoral Science Foundation of China(2023M732812 to T.L.).

摘　　要：Tumor microenvironment(TME),as the“soil”of tumor growth and metastasis,exhibits significant differences from normal physiological conditions.However,how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge.Herein,an innovative nanoreactor(AH@MBTF)is developed to utilize the apparent differences(copper concentration and H_(2)O_(2)level)between tumor cells and normal cells to eliminate primary tumor based on H_(2)O_(2)-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation.This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea(BTU),triphenylphosphine(TPP),and folic acid(FA),while being co-loaded with horseradish peroxidase(HRP)and its substrate ABTS.During therapy,the BTU moieties on AH@MBTF could capture excessive copper(highly correlated with tumor metastasis),presenting exceptional anti-metastasis activity.Simultaneously,the complexation between BTU and copper triggers the formation of cuprous ions,which further react with H_(2)O_(2)to generate cytotoxic hydroxyl radical(•OH),inhibiting tumor growth via che-modynamic therapy.Additionally,the stepwise targeting of FA and TPP guides AH@MBTF to accurately accu-mulate in tumor mitochondria,containing abnormally high levels of H_(2)O_(2).As a catalyst,HRP mediates the oxidation reaction between ABTS and H_(2)O_(2)to yield activated ABTS•^(+).Upon 808 nm laser irradiation,the activated ABTS•^(+)performs tumor-specific photothermal therapy,achieving the ablation of primary tumor by raising the tissue temperature.Collectively,this intelligent nanoreactor possesses profound potential in inhib-iting tumor progression and metastasis.

关 键 词：NANOREACTOR H_(2)O_(2)-dependent Photothermal-chemodynamic therapy Copper depletion Tumor metastasis inhibition 

分 类 号：R730.5[医药卫生—肿瘤] R318[医药卫生—临床医学]