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.

• Authors: Jayanta Bhattacharyya, Xiu-Rong Ren, Robert A Mook, Jiangbo Wang, Ivan Spasojevic, Richard T Premont, Xinghai Li, Ashutosh Chilkoti, Wei Chen
• Journal: Nanoscale (Nanoscale) Vol. 9 Issue 34 Pg. 12709-12717 (Aug 31 2017) ISSN: 2040-3372 [Electronic] England
• PMID: 28828438 (Publication Type: Journal Article)

Chemical References

• Peptides
• Niclosamide

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Colonic Neoplasms (drug therapy)
• Diabetes Mellitus, Type 2
• Humans
• Male
• Mice, Nude
• Nanoparticles
• Niclosamide (pharmacology)
• Peptides (pharmacology)
• Wnt Signaling Pathway (drug effects)
• Xenograft Model Antitumor Assays