title: Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide.
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.
authors.affiliation: Cancer Epigenetics, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia. pilar.blancafort@uwa.edu.au.
authors.forename: A
authors.initials: A
authors.lastname: Sorolla
authors.affiliation: School of Chemistry & Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. swaminatha.iyer@uwa.edu.au.
authors.forename: D
authors.initials: D
authors.lastname: Ho
authors.affiliation: Cancer Epigenetics, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia. pilar.blancafort@uwa.edu.au.
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.affiliation: School of Chemistry & Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. swaminatha.iyer@uwa.edu.au.
authors.forename: C W
authors.initials: CW
authors.lastname: Evans
authors.affiliation: School of Chemistry & Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. swaminatha.iyer@uwa.edu.au.
authors.forename: C F G
authors.initials: CF
authors.lastname: Ormonde
authors.affiliation: Cancer Epigenetics, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia. pilar.blancafort@uwa.edu.au.
authors.forename: R
authors.initials: R
authors.lastname: Rashwan
authors.affiliation: School of Chemistry & Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. swaminatha.iyer@uwa.edu.au.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: School of Chemistry & Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. swaminatha.iyer@uwa.edu.au.
authors.forename: K Swaminathan
authors.initials: KS
authors.lastname: Iyer
authors.affiliation: Cancer Epigenetics, Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia. pilar.blancafort@uwa.edu.au.
authors.forename: P
authors.initials: P
authors.lastname: Blancafort
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D018398:Homeodomain Proteins / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles; D010455:Peptides; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; C513076:EN1 protein, human; D018398:Homeodomain Proteins; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel