학술논문
CD44-Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem-Like Cells: A Novel Hyaluronic Acid-Based Drug Delivery System.
Document Type
Article
Author
Source
Subject
*GLYCOPROTEINS
*DOCETAXEL
*TARGETED drug delivery
*CANCER stem cells
*HYALURONIC acid
*DRUG delivery systems
*NUCLEAR magnetic resonance spectroscopy
*
*
*
*
*
*
Language
ISSN
1747-0277
Abstract
A CD44-targeted macromolecular conjugate of docetaxel was prepared via a pH-sensitive linkage to hyaluronic acid and was characterized using NMR, gel permeation chromatography, and differential scanning calorimetry. The conjugated species were further evaluated in terms of drug release, cytotoxicity, cellular uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular microscopic studies revealed that CD44-expressing cells including MCF-7 cancer stem cells and MDA-MB-231 metastatic breast cancer cells had internalized the conjugates via a selective receptor-mediated mechanism, leading to cell cycle arrest in the G2/M phase. Hyaluronic acid-docetaxel conjugates showed specific toxicity only in CD44-expressing cells in vitro, along with a decreased risk of neutropenia and dose-dependent mortality in vivo. Hyaluronic acid-drug conjugates represent a promising and efficient platform for solubilization of sparingly soluble molecules as well as active and selective targeted delivery to cancer cells and cancer stem cells. [ABSTRACT FROM AUTHOR]