Galactose-Containing Polymer-DOX Conjugates for Targeting Drug Delivery.

A novel multifunctional drug delivery system was fabricated by conjugating galactose-based polymer, methoxy-poly(ethylene glycol)-block-poly(6-O-methacryloyl-D-galactopyranose) (mPEG-b-PMAGP) with doxorubicin (DOX) via an acid-labile carbamate linkage. The mPEG-b-PMAGP-co-DOX nanoparticles were spherical in shape, and the diameter determined by dynamic light scattering (DLS) was 54.84 ± 0.58 nm, larger than that characterized by transmission electron microscopy (TEM). The in vitro drug release profiles were studied, and the release of DOX from the nanoparticles was pH-responsive. The cellular uptake behavior of free-DOX and mPEG-b-PMAGP-co-DOX nanoparticles by asialoglycoprotein (ASGP) receptor-positive cancer cell line (HepG2) and ASGP receptor-negative cancer cell lines (MCF-7 and A549 cells) was evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM), respectively. The mPEG-b-PMAGP-co-DOX nanoparticles which contain galactose functional groups exhibited higher cellular uptake behavior via ASGP receptor-mediated endocytosis in HepG2 cells than in other two cancer cells. The in vitro cytotoxicity assay manifested that the mPEG-b-PMAGP-co-DOX nanoparticles exhibited higher anticancer efficacy against HepG2 cells than MCF-7 cells. These results indicated that the multifunctional mPEG-b-PMAGP-co-DOX nanoparticles possessing pH-responsible and hepatoma-targeting function have great potential to be used as a targeting drug delivery system for hepatoma therapy.