title: Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles.
abstract: Treatment with chemotherapy such as docetaxel (DTX) is associated with significant toxicity and tumour recurrence. In this study, we developed DTX-entrapped core-cross-linked polymeric micelles (DTX-CCL-PMs, 66 nm size) by covalently conjugating DTX to CCL-PMs via a hydrolysable ester bond. The covalent conjugation allowed for sustained release of DTX under physiological conditions in vitro. In vivo, DTX-CCL-PMs demonstrated superior therapeutic efficacy in mice bearing MDA-MB-231 tumour xenografts as compared to the marketed formulation of DTX (Taxotere(®)). Strikingly, a single intravenous injection of DTX-CCL-PMs enabled complete regression of both small (∼150 mm(3)) and established (∼550 mm(3)) tumours, leading to 100% survival of the animals. These remarkable antitumour effects of DTX-CCL-PMs are attributed to its enhanced tumour accumulation and anti-stromal activity. Furthermore, DTX-CCL-PMs exhibited superior tolerability in healthy rats as compared to Taxotere. These preclinical data strongly support clinical translation of this novel nanomedicinal product for the treatment of cancer.
authors.affiliation: Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands; Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
authors.forename: Cristianne J
authors.initials: CJ
authors.lastname: Rijcken
authors.affiliation: Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands; Cancer Centre Karolinska, Karolinska Institutet, Stockholm SE-171 76, Sweden. Electronic address: j.prakash@utwente.nl.
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D051379:Mice; D008823:Micelles; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel
keywords: Antitumour efficacy; Breast cancer; Docetaxel; Polymeric micelles; Tumour targeting