Issue 22, 2019

A selenium-containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy

Abstract

Early detection and effective treatment are essential for the management of breast cancer, especially for triple-negative breast cancer (TNBC). However, current imaging methods and treatment strategies are ineffective because of the lack of efficient biomarkers and molecular targets. Thus, identifying novel biomarkers and their corresponding ligands is critical for controlling breast cancer. Histone deacetylase 6 (HDAC6) has emerged as a valid target for cancer therapy owing to its selective tumor inhibition and fewer side effects compared to pan-HDAC- and HDAC1–3 isoform-selective inhibitors. Here, a HDAC6-selective inhibitor, SelSA, was developed by utilizing a selenocyanide moiety instead of the conventional hydroxamic acid core, which showed 112-fold and 128-fold selective binding affinity for HDAC6 relative to HDAC1 and HDAC8. In vitro studies demonstrated that FITC-SelSA was specifically uptaken by both ERα(+) MCF-7 and TNBC MDA-MB-231 cells, with primarily cytoplasmic localization. SelSA reactivated ERα expression and sensitized TNBC cell responses to the antagonist tamoxifen, and displayed potent antitumor effects against both MCF-7 and MDA-MB-231 cells in vitro and tumor xenografts in vivo with no obvious side effects. Moreover, in in vivo near-infrared fluorescence imaging to assess SelSA biodistribution, the IRDye800CW-SelSA probe exhibited specific tumor targeting ability with high tumor-to-normal tissue contrast. The in vivo tumor treatment study revealed that SelSA possessed improved treatment efficacy and fewer side effects in both ERα(+) and TNBC tumors, compared to pan-HDAC inhibitors. Overall, our study indicated that the HDAC6 inhibitor SelSA is a highly promising candidate for targeted breast cancer imaging and therapy with clinical translational potential.

Graphical abstract: A selenium-containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy

Supplementary files

Article information

Article type
Paper
Submitted
26 2月 2019
Accepted
02 4月 2019
First published
18 4月 2019

J. Mater. Chem. B, 2019,7, 3528-3536

A selenium-containing selective histone deacetylase 6 inhibitor for targeted in vivo breast tumor imaging and therapy

C. Tang, Y. Du, Q. Liang, Z. Cheng and J. Tian, J. Mater. Chem. B, 2019, 7, 3528 DOI: 10.1039/C9TB00383E

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