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

Q. Hu; Cristianne J. Rijcken; Ruchi Bansal; Wim E. Hennink; Gerrit 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

Q. Hu, Cristianne J. Rijcken, Ruchi Bansal, Wim E. Hennink, Gerrit Storm, Jai Prakash

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

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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 mm3) and established (∼550 mm3) 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	Undefined
Pages (from-to)	370-378
Journal	Biomaterials
Volume	53
DOIs	https://doi.org/10.1016/j.biomaterials.2015.02.085
Publication status	Published - 2015

Keywords

METIS-310435
IR-95812

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10.1016/j.biomaterials.2015.02.085

Hu et al. Biomaterials 2015
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Cite this

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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, 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{\textregistered}). Strikingly, a single intravenous injection of DTX-CCL-PMs enabled complete regression of both small (∼150 mm3) and established (∼550 mm3) 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 = "METIS-310435, IR-95812",

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

year = "2015",

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

language = "Undefined",

volume = "53",

pages = "370--378",

journal = "Biomaterials",

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T1 - Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles

AU - Hu, Q.

AU - Rijcken, Cristianne J.

AU - Bansal, Ruchi

AU - Hennink, Wim E.

AU - Storm, Gerrit

AU - Prakash, Jai

PY - 2015

Y1 - 2015

N2 - 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 mm3) and established (∼550 mm3) 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

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, 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 mm3) and established (∼550 mm3) 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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KW - IR-95812

U2 - 10.1016/j.biomaterials.2015.02.085

DO - 10.1016/j.biomaterials.2015.02.085

M3 - Article

VL - 53

SP - 370

EP - 378

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -