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

A. Sorolla, Diwei Ho, E. Wang, Cameron Evans, Callum Ormonde, R. Rashwan, Ruhani Singh, Killugudi Swaminatha Iyer, Pilar Blancafort

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

© 2016 The Royal Society of Chemistry.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.
Original languageEnglish
Pages (from-to)9343-9353
JournalNanoscale
Volume8
Issue number17
DOIs
Publication statusPublished - 11 Apr 2016

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