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 

机构地区：[1]State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu,610041,China [2]Key Laboratory of Xinjiang Phytomedicine Resource and Utilization,Ministry of Education,School of Pharmacy,Shihezi University,Shihezi,Xinjiang,832002,China [3]Department of Neurosurgery,West China Hospital,Sichuan University,Chengdu,610041,China [4]Department of Radiation Oncology,Cancer Center,West China Hospital,Sichuan University,Chengdu,610041,China

出　　处：《Journal of Pharmaceutical Analysis》2023年第1期99-109,共11页药物分析学报（英文版）

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).

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.

关 键 词：Carrier-free nanoreactor Ferroptosis MICROTUBULE Colorectal cancer 

分 类 号：R965[医药卫生—药理学]