Issue 6, 2018

Nanodiamond-based non-canonical autophagy inhibitor synergistically induces cell death in oxygen-deprived tumors

Abstract

The tumor microenvironment (TME) plays a key role in tumor progression and has been actively explored as a promising target for cancer therapy. One key challenge in TME-based therapy lies in the presence of high levels of autophagy under oxygen-deprived conditions (referred to as hypoxia), which is an evolution-based adaptive strategy of cancer cells to facilitate tumor growth and metastasis. Here, we utilize a type of biocompatible nanoparticle, nanodiamonds (NDs), to block autophagic flux in cultured cells and xenograft tumors. Whereas ND treatment has little effect on the cell viability under normal oxygen levels (referred to as normoxia), it selectively induces programmed cell death in hypoxic cancer cells, thus showing specificity for in vivo tumors. Unlike clinically used autophagy inhibitors that demonstrate general toxicity and activate HIF signaling, we find that NDs selectively inhibit autophagic degradation with minimal impairment of lysosomal functions and do not affect HIF activity. Significantly, intravenous injection of NDs acts synergistically with Sorafenib, an anti-angiogenic drug used clinically for cancer therapy, to inhibit the growth of hepatocellular carcinoma in mice. This distinct mechanism of NDs opens a new door for targeted anti-angiogenic therapy of solid tumors.

Graphical abstract: Nanodiamond-based non-canonical autophagy inhibitor synergistically induces cell death in oxygen-deprived tumors

Supplementary files

Article information

Article type
Communication
Submitted
20 авг 2018
Accepted
13 сеп 2018
First published
13 сеп 2018

Mater. Horiz., 2018,5, 1204-1210

Nanodiamond-based non-canonical autophagy inhibitor synergistically induces cell death in oxygen-deprived tumors

N. Chen, Y. Han, Y. Luo, Y. Zhou, X. Hu, Y. Yu, X. Xie, M. Yin, J. Sun, W. Zhong, Y. Zhao, H. Song and C. Fan, Mater. Horiz., 2018, 5, 1204 DOI: 10.1039/C8MH00993G

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