Hyaluronic acid conjugated micelles possessing CD44 targeting potential for gene delivery.

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.