Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles

Qizhi Hu; Cristianne J Rijcken; Ruchi Bansal; Wim E Hennink; Gert Storm; Jai Prakash

doi:10.1016/j.biomaterials.2015.02.085

Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles

Biomaterials. 2015:53:370-8. doi: 10.1016/j.biomaterials.2015.02.085. Epub 2015 Mar 18.

Authors

Qizhi Hu¹, Cristianne J Rijcken², Ruchi Bansal³, Wim E Hennink⁴, Gert Storm⁵, Jai Prakash⁶

Affiliations

¹ 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.
² Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
³ Department of Biomaterials Science and Technology, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede 7500AE, The Netherlands.
⁴ Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
⁵ 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.
⁶ 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.

PMID: 25890735
DOI: 10.1016/j.biomaterials.2015.02.085

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.

Keywords: Antitumour efficacy; Breast cancer; Docetaxel; Polymeric micelles; Tumour targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / drug therapy*
Cell Line, Tumor
Docetaxel
Female
Humans
Mice
Micelles*
Rats
Rats, Sprague-Dawley
Taxoids / therapeutic use*

Substances

Antineoplastic Agents
Micelles
Taxoids
Docetaxel