Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor

作     者：Min Mu Xiaoyan Liang Na Zhao Di Chuan Bo Chen Shasha Zhao Guoqing Wang Rangrang Fan Bingwen Zou Bo Han Gang Guo Min Mu;Xiaoyan Liang;Na Zhao;Di Chuan;Bo Chen;Shasha Zhao;Guoqing Wang;Rangrang Fan;Bingwen Zou;Bo Han;Gang Guo

作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu610041China Key Laboratory of Xinjiang Phytomedicine Resource and UtilizationMinistry of EducationSchool of PharmacyShihezi UniversityShiheziXinjiang832002China Department of NeurosurgeryWest China HospitalSichuan UniversityChengdu610041China Department of Radiation OncologyCancer CenterWest China HospitalSichuan UniversityChengdu610041China 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2023年第13卷第1期

页      面：99-109页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床] 

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:31971308,81960769,and U1903211) National S&T Major Project(Grant No.:2019ZX09301-147),Luzhou Science and Technology Plan(Grant No.:2018CDLZ10) Sichuan Science and Technology Program(Grant No.:2021YFS0081). 

主　　题：Carrier-free nanoreactor Ferroptosis Microtubule Colorectal cancer 

摘      要：Traditional microtubule inhibitors fail to significantly enhance+e effect of colorectal cancer;hence,new and efficient strategies are necessary.In+is study,a supramolecular nanoreactor(DOC@TA-Fe^(3+))based on tannic acid(TA),iron ion(Fe^(3+)),and docetaxel(DOC)wi+microtubule inhibition,reactive oxygen species(ROS)generation,and gluta+ione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,+e DOC@TA-Fe^(3+)nanoreactor escapes from+e lysosomes to release payloads.+e subsequent Fe^(3+)/Fe^(2+)conversion mediated by TA reducibility can trigger+e Fenton reaction to enhance+e ROS concentration.Additionally,Fe^(3+)can consume gluta+ione to repress+e activity of GPX4 to induce ferroptosis.Meanwhile,+e released DOC controls microtubule dynamics to activate+e apoptosis pa+way.+e superior in vivo antitumor efficacy of DOC@TA-Fe^(3+)nanoreactor in terms of tumor grow+inhibition and improved survival is verified in CT26 tumor-bearing mouse model.+erefore,+e nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer+erapy.