Issue 34, 2017

Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth

Abstract

Abnormal Wnt activity is a major mechanism responsible for many diseases, including cancer. Previously, we reported that the anthelmintic drug Niclosamide (NIC) inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth. Although the pharmacokinetic properties of NIC are appropriate for use as an anthelmintic agent, its low solubility, low bioavailability and low systemic exposure limit its usefulness in treating systemic diseases. To overcome these limitations, we conjugated NIC to recombinant chimeric polypeptides (CPs), and the CP-NIC conjugate spontaneously self-assembled into sub-100 nm near-monodisperse nanoparticles. CP-NIC nanoparticles delivered intravenously act as a pro-drug of NIC to dramatically increase exposure of NIC compared to dosing with free NIC. CP-NIC improved anti-tumor activity compared to NIC in a xenograft model of human colon cancer. Because NIC has multiple biological activities, CP-NIC could be used for treatment of multiple diseases, including cancer, bacterial and viral infection, type II diabetes, NASH and NAFLD.

Graphical abstract: Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth

Supplementary files

Article information

Article type
Paper
Submitted
20 Mar 2017
Accepted
31 Jul 2017
First published
01 Aug 2017

Nanoscale, 2017,9, 12709-12717

Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth

J. Bhattacharyya, X. Ren, R. A. Mook, J. Wang, I. Spasojevic, R. T. Premont, X. Li, A. Chilkoti and W. Chen, Nanoscale, 2017, 9, 12709 DOI: 10.1039/C7NR01973D

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