title: Mixed Micelles for Targeted and Efficient Doxorubicin Delivery to Multidrug-Resistant Breast Cancer Cells.
abstract: 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.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Heesun
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D061986:MCF-7 Cells; D008823:Micelles; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D011409:Propylene Glycols / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D008823:Micelles; D011108:Polymers; D011409:Propylene Glycols; C480965:pluronic L61; D020442:Poloxamer; C012504:polypropylene glycol; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: doxorubicin; hyaluronic acid; mixed micelle; multidrug-resistant cell; pluronic L61; poly(propylene glycol)