Mixed Micelles for Targeted and Efficient Doxorubicin Delivery to Multidrug-Resistant Breast Cancer Cells

被引:18
|
作者
Jung, Heesun [1 ]
Mok, Hyejung [1 ]
机构
[1] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea
基金
新加坡国家研究基金会;
关键词
doxorubicin; hyaluronic acid; mixed micelle; multidrug-resistant cell; pluronic L61; poly(propylene glycol); CONJUGATE MICELLES; POLYMERIC MICELLES; DRUG; MDR; NANOPARTICLES; PLURONIC(R); HYALURONAN; REVERSAL;
D O I
10.1002/mabi.201500381
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
For efficient treatment of multidrug-resistance (MDR) breast cancer cells, design of biocompatible mixed micelles with diverse functional moieties and superior stability is needed for targeted delivery of chemical drugs. In this study, polypropylene glycol (PPG)-grafted hyaluronic acid (HA) copolymers (PPG-g-HA) are used to make mixed micelles with different amounts of pluronic L61, named PPG-g-HA/L61 micelles. Optimized PPG-g-HA/L61 micelles with 3% pluronic L61 exhibit great stability in aqueous solution, superior biocompatibility, and significantly increased uptake into MCF-7 MDR cells via HA-CD44-specific interactions when compared to free doxorubicin (DOX) and other types of micelles. In addition, DOX in PPG-g-HA/L61 micelles with 3% pluronic L61 have toxicity in MCF-7 MDR cells but significantly lower toxicity in fibroblast L929 cells compared to free DOX. Thus, PPG-g-HA/L61 micelles with 3% pluronic L61 content can be a promising nanocarrier to overcome MDR and release DOX in a hyaluronidase-sensitive manner without any toxicity to normal cells.
引用
收藏
页码:748 / 758
页数:11
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