Synthesis, characterization, and in vitro evaluation of two synergistic anticancer drug-containing hepatoma-targeting micelles formed from amphiphilic random copolymer

In this study we fabricated and characterized novel galactose-functionalized multidrug-containing nanoparticles, and in vitro evaluated their enhanced anti-tumorous cell cytotoxicity and hepatoma-targeting ability for the controlled delivery of two synergistic anticancer drugs. A chemo-enzymatic synthesis strategy was used to prepare a galactose-functionalized amphiphilic random copolymer containing cytarabine (Ara-C) and fluorodeoxyuridine (FUDR). The formed nanoparticles were characterized for their critical aggregation concentration (CAC), morphology, cellular uptake, cell cytotoxicity, hepatoma targeting ability and controlled drug release. The micellization ability of the galactose-functionalized amphiphilic random copolymer was confirmed. In vitro drug release studies showed that the two anticancer agents could be simultaneously released from the nanoparticles. Cellular uptake assay and cytotoxicity tests demonstrated that these nanoparticles could be effectively internalized by HepG2 cells and had an evident targeting function through the selective recognition of galactose pendants of the copolymer by ASGP-R of HepG2 cells. Furthermore, the enhanced anti-tumorous cell cytotoxicity indicated the combination of Ara-C, FUDR and D-galactose in one copolymer may have a better synergistic effect. This encouraging finding illustrated that the D-galactose functionalized nanoparticles could be used as a novel potential hepatoma-targeting multidrug delivery vehicle.