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

Qizhi Hu, Cristianne J. Rijcken, Ruchi Bansal, Wim E. Hennink, Gert Storm, Jai Prakash^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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, 66nm 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 invitro. Invivo, 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 (~150mm3) and established (~550mm3) 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.

Original language	English
Pages (from-to)	370-378
Number of pages	9
Journal	Biomaterials
Volume	53
DOIs	https://doi.org/10.1016/j.biomaterials.2015.02.085
Publication status	Published - 1 Jan 2015

Keywords

Antitumour efficacy
Breast cancer
Docetaxel
Polymeric micelles
Tumour targeting

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10.1016/j.biomaterials.2015.02.085

micellesFinal published version, 1.46 MBLicence: Taverne

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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, 66nm 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 invitro. Invivo, DTX-CCL-PMs demonstrated superior therapeutic efficacy in mice bearing MDA-MB-231 tumour xenografts as compared to the marketed formulation of DTX (Taxotere{\textregistered}). Strikingly, a single intravenous injection of DTX-CCL-PMs enabled complete regression of both small (~150mm3) and established (~550mm3) 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",

author = "Qizhi Hu and Rijcken, {Cristianne J.} and Ruchi Bansal and Hennink, {Wim E.} and Gert Storm and Jai Prakash",

year = "2015",

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doi = "10.1016/j.biomaterials.2015.02.085",

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AU - Rijcken, Cristianne J.

AU - Bansal, Ruchi

AU - Hennink, Wim E.

AU - Storm, Gert

AU - Prakash, Jai

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AB - 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, 66nm 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 invitro. Invivo, 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 (~150mm3) and established (~550mm3) 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.

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

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Keywords

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