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Issue 17, 2016
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Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

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Abstract

Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.

Graphical abstract: Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

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Supplementary files

Article information


Submitted
25 Nov 2015
Accepted
09 Apr 2016
First published
11 Apr 2016

Nanoscale, 2016,8, 9343-9353
Article type
Paper
Author version available

Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

A. Sorolla, D. Ho, E. Wang, C. W. Evans, C. F. G. Ormonde, R. Rashwan, R. Singh, K. S. Iyer and P. Blancafort, Nanoscale, 2016, 8, 9343
DOI: 10.1039/C5NR08331A

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