Issue 17, 2023

GPX4 inhibition synergistically boosts mitochondria targeting nanoartemisinin-induced apoptosis/ferroptosis combination cancer therapy

Abstract

Artemisinin, originally used for its antimalarial activity, has received much attention in recent years for cancer therapy. The anticancer mechanisms of artemisinin are complicated and debatable. Challenges in the delivery of artemisinin also persist because the anticancer effect of artemisinin alone is often not satisfactory when used with traditional nanocarriers. We herein report the mitochondrial delivery of artemisinin with extremely high anticancer capacity. The action mode of artemisinin in the mitochondria of cancer cells includes heme-participating and oxygen-independent conversion of artemisinin into a carbon-centered radical, which is partly converted into ROS in the presence of molecular oxygen. We reveal that artemisinin alone in the mitochondria can induce strong cancer cell apoptosis. In addition, due to the weak inhibition of GPX4 activity by artemisinin, weak ferroptosis is also observed. We further discover that GPX4 activity in MCF-7 cells is greatly inhibited by RSL3 to synergistically enhance the anticancer capacity of artemisinin via enhancing ferroptosis. The synergistic anticancer activity of artemisinin and RSL3 in the mitochondria not only improves cancer cell-killing ability, but also inhibits the re-proliferation of residual cancer cells. This study provides a new insight into developing highly efficient and practical artemisinin nanomedicines for cancer therapy.

Graphical abstract: GPX4 inhibition synergistically boosts mitochondria targeting nanoartemisinin-induced apoptosis/ferroptosis combination cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
11 Apr 2023
Accepted
03 Jul 2023
First published
04 Jul 2023

Biomater. Sci., 2023,11, 5831-5845

GPX4 inhibition synergistically boosts mitochondria targeting nanoartemisinin-induced apoptosis/ferroptosis combination cancer therapy

H. Yu, J. Li, K. Deng, W. Zhou, K. Li, C. Wang, Q. Wang, M. Wu and S. Huang, Biomater. Sci., 2023, 11, 5831 DOI: 10.1039/D3BM00601H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements