title: Hyaluronic acid conjugated micelles possessing CD44 targeting potential for gene delivery.
abstract: The high- and low-molecular weight hyaluronic acid (HHA and LHA) were used to conjugate with PLGA-PEG copolymers which were applied to encapsulate DOTAP/pDNA (D/P) lipoplex as a CD44-targeted micelle delivery system. The size and zeta potential of DNA loaded micelles were measured. The cytotoxicity and cellular transfection of DNA loaded micelles were performed in CD44-positive MDA-MB-231 and MCF-7 cancer cells and CD44-negative HepG2 cells. The endocytosis mechanism of micelles was investigated further. The DNA loaded HA-conjugated micelles possessed negative-charged character which prevented erythrocytes from agglutination. Both LHA-PEG-PLGA and HHA-PEG-PLGA micelles had comparable cellular viability in L929 normal cells. The cellular transfection of HHA-PEG-PLGA micelles was much higher than of LHA-PEG-PLGA micelles in CD44-positive cells. The specific and strong binding of HHA to CD44-positive cells resulted in the cellular transfection of HHA-PEG-PLGA micelles in CD44-positive cells significantly higher than in CD44-negative cells.
authors.affiliation: Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan; Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: wjlin@ntu.edu.tw.
authors.forename: Wen Jen
authors.initials: WJ
authors.lastname: Lin
authors.affiliation: Graduate Institute of Pharmaceutical Sciences, School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Ming-Jium
authors.initials: MJ
authors.lastname: Shieh
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D005229:Fatty Acids, Monounsaturated; D018014:Gene Transfer Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry*; D008823:Micelles; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D000644:Quaternary Ammonium Compounds
chemical_list: C497483:CD44 protein, human; D005229:Fatty Acids, Monounsaturated; D018960:Hyaluronan Receptors; D008823:Micelles; D000644:Quaternary Ammonium Compounds; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
keywords: CD44 receptor; Gene delivery; Hyaluronic acid; Poly(lactide-co-glycolide)