title: In vivo and ex vivo proofs of concept that cetuximab conjugated vitamin E TPGS micelles increases efficacy of delivered docetaxel against triple negative breast cancer.
abstract: In this study we examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. Here, we developed docetaxel-loaded vitamin E D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles, of which the surface modified with cetuximab ligands for targeting epidermal growth factor receptors (EGFR) that are overexpressed in MDA-MB-231 breast cancer cells. The targeting micelles accumulated in the tumours immediately after the intravenous injection and retained for at least 24 h. The successful delivery of docetaxel into the tumours by the targeting micelles was shown by the greater degree of tumour growth inhibition than that for Taxotere(®) after the 15-day treatment. Furthermore, the explanted tumour culture study involving gene analysis and immunohistochemistry staining indicated that the in vivo micelle treatment induced cell cycle arrest and attenuated cell proliferation. In addition, the targeting and non-targeting micellar formulations brought about anti-angiogenesis and anti-migration effects. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGFR-overexpressing MDA-MB-231 tumours.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Rajaletchumy Veloo
authors.initials: RV
authors.lastname: Kutty
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Sing Ling
authors.initials: SL
authors.lastname: Chia
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
authors.forename: Magdiel I
authors.initials: MI
authors.lastname: Setyawati
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Madaswamy S
authors.initials: MS
authors.lastname: Muthu
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; International Joint Cancer Institute, The Second Military Medical University, 800, Xiang Yin Road, Shanghai 200433, PR China. Electronic address: chefss@nus.edu.sg.
authors.forename: Si-Shen
authors.initials: SS
authors.lastname: Feng
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore; NUS Graduate School for Integrative Science and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. Electronic address: cheltwd@nus.edu.sg.
authors.forename: David Tai
authors.initials: DT
authors.lastname: Leong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D016513:Mice, SCID; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; D011092:Polyethylene Glycols; C014225:tocophersolan; D000068818:Cetuximab
keywords: Biodegradable polymers; Cancer nanotechnology; Drug targeting; Molecular biomaterials; Nanomedicine; Pharmaceutical nanotechnology