Complete regression of breast tumour with a single dose of docetaxel-entrapped core-cross-linked polymeric micelles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25890735.
- Also identified by DOI 10.1016/j.biomaterials.2015.02.085.
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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 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.
Medical subject headings
- Antineoplastic Agents
- Breast Neoplasms
- Micelles
- Taxoids