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

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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 languageUndefined
Pages (from-to)370-378
JournalBiomaterials
Volume53
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-310435
  • IR-95812

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{\circledR}). 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",
issn = "0142-9612",
publisher = "Elsevier",

}

Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles. / Hu, Q.; Rijcken, Cristianne J.; Bansal, Ruchi; Hennink, Wim E.; Storm, Gerrit; Prakash, Jai.

In: Biomaterials, Vol. 53, 2015, p. 370-378.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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

KW - METIS-310435

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 -