Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

作     者：Haifeng Yuan Yan Zhao Chan Yang Cheng Zhang Yue Yang Hongmin Meng Shuangyan Huan Guosheng Song Xiaobing Zhang Haifeng Yuan;Yan Zhao;Chan Yang;Cheng Zhang1;Yue Yang;Hongmin Meng;Shuangyan Huan;Guosheng Song;Xiaobing Zhang

作者机构：State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China College of ChemistryZhengzhou UniversityZhengzhou 450001China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2020年第63卷第7期

页      面：924-935页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100602[医学-中西医结合临床] 10[医学] 0702[理学-物理学] 

基　　金：supported by the National Natural Science Foundation of China (51872088  21977027  21804039  21675043  21890744) 

主　　题：coordination nanoplatform metallodrug chemodynamic therapy circular catalysis drug delivery 

摘      要：For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.