Available online 7 October 2022

A supramolecular nanoreactor ([email protected]3+) based on TA, Fe3+, and DOC is prepared.

Fe3+/Fe2+ conversion mediated by TA reducibility can trigger the Fenton reaction.

[email protected]3+ can serve as an efficient inducer of apoptosis and ferroptosis for tumor therapy.

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 ([email protected]3+) 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 [email protected]3+ 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 glutathione 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 [email protected]3+ 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.

Carrier-free nanoreactor

ferroptosis

microtubule

colorectal cancer

© 2022 The Author(s). Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.