Graft copolymer composed
hyaluronic acid (HA) and
poly(D,L-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of
tumor cells. The carboxylic end of PLGA was conjugated with
hexamethylenediamine (
HMDA) to have
amine end group in the end of chain (PLGA-
amine). PLGA-
amine was coupled with
carboxylic acid of HA. Self-assembled polymeric
micelles of HAgLG have spherical morphologies and their sizes were around 50-200 nm.
Doxorubicin (DOX)-incorporated polymeric
micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric
enzyme hyaluronidase. To assess targetability of polymeric
micelles, CD44-positive HepG2 cells were employed treated with
fluorescein isothiocyanate (
FITC)-labeled polymeric
micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric
micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric
micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric
micelles of HaLG polymeric
micelles have targetability against CD44 receptor of
tumor cells. We suggest HAgLG polymeric
micelles as a promising candidate for specific drug targeting.