Journal
MACROMOLECULAR BIOSCIENCE
Volume 16, Issue 5, Pages 748-758Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201500381
Keywords
doxorubicin; hyaluronic acid; mixed micelle; multidrug-resistant cell; pluronic L61; poly(propylene glycol)
Funding
- Global Innovative Research Center (GiRC) program [NRF-2012K1A1A2A01056094]
- National Research Foundation (NRF) - Ministry of Education, Science and Technology, Republic of Korea [NRF-2014R1A2A1A11049772]
- National Research Foundation of Korea [2014R1A2A1A11049772, 2012K1A1A2A01056094] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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