Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor
- Author:
Min MU
1
;
Xiaoyan LIANG
;
Na ZHAO
;
Di CHUAN
;
Bo CHEN
;
Shasha ZHAO
;
Guoqing WANG
;
Rangrang FAN
;
Bingwen ZOU
;
Bo HAN
;
Gang GUO
Author Information
1. State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu,610041,China
- Keywords:
Carrier-free nanoreactor;
Ferroptosis;
Microtubule;
Colorectal cancer
- From:
Journal of Pharmaceutical Analysis
2023;13(1):99-109
- CountryChina
- Language:Chinese
-
Abstract:
Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer;hence,new and efficient strategies are necessary.In this study,a supramolecular nanoreactor(DOC@TA-Fe3+)based on tannic acid(TA),iron ion(Fe3+),and docetaxel(DOC)with microtubule inhibition,reactive oxygen species(ROS)generation,and glutathione peroxidase 4(GPX4)inhibition,is prepared for ferroptosis/apoptosis treatment.After internalization by CT26 cells,the DOC@TA-Fe3+nanoreactor escapes from the lysosomes to release payloads.The subsequent Fe3+/Fe2+conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration.Additionally,Fe3+can consume gluta-thione to repress the activity of GPX4 to induce ferroptosis.Meanwhile,the released DOC controls microtubule dynamics to activate the apoptosis pathway.The superior in vivo antitumor efficacy of DOC@TA-Fe3+nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model.Therefore,the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.
