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

Publication ,  Journal Article
Bhattacharyya, J; Ren, X-R; Mook, RA; Wang, J; Spasojevic, I; Premont, RT; Li, X; Chilkoti, A; Chen, W
Published in: Nanoscale
August 31, 2017

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.

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Published In

Nanoscale

DOI

EISSN

2040-3372

Publication Date

August 31, 2017

Volume

9

Issue

34

Start / End Page

12709 / 12717

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Wnt Signaling Pathway
  • Peptides
  • Niclosamide
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice, Nude
  • Male
  • Humans
  • Diabetes Mellitus, Type 2
 

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Bhattacharyya, J., Ren, X.-R., Mook, R. A., Wang, J., Spasojevic, I., Premont, R. T., … Chen, W. (2017). Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth. Nanoscale, 9(34), 12709–12717. https://doi.org/10.1039/c7nr01973d
Bhattacharyya, Jayanta, Xiu-Rong Ren, Robert A. Mook, Jiangbo Wang, Ivan Spasojevic, Richard T. Premont, Xinghai Li, Ashutosh Chilkoti, and Wei Chen. “Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth.Nanoscale 9, no. 34 (August 31, 2017): 12709–17. https://doi.org/10.1039/c7nr01973d.
Bhattacharyya J, Ren X-R, Mook RA, Wang J, Spasojevic I, Premont RT, et al. Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth. Nanoscale. 2017 Aug 31;9(34):12709–17.
Bhattacharyya, Jayanta, et al. “Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth.Nanoscale, vol. 9, no. 34, Aug. 2017, pp. 12709–17. Pubmed, doi:10.1039/c7nr01973d.
Bhattacharyya J, Ren X-R, Mook RA, Wang J, Spasojevic I, Premont RT, Li X, Chilkoti A, Chen W. Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth. Nanoscale. 2017 Aug 31;9(34):12709–12717.
Journal cover image

Published In

Nanoscale

DOI

EISSN

2040-3372

Publication Date

August 31, 2017

Volume

9

Issue

34

Start / End Page

12709 / 12717

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Wnt Signaling Pathway
  • Peptides
  • Niclosamide
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice, Nude
  • Male
  • Humans
  • Diabetes Mellitus, Type 2