Construction of efficacious hepatoma-targeted nanomicelles non-covalently functionalized with galactose for drug delivery

Polymeric micelles with surface immobilized galactose (Gal) are promising candidates for hepatoma-targeted drug delivery. Herein, a novel hepatoma-targeted micellar system was prepared through the non-covalent attachment of Gal to the micellar surface. A series of pH-responsive methoxyl poly(ethylene glycol)-b-poly(β-amino ester) (MPEG-PBAE) consisting of a hydrophobic alkyl chain were easily synthesized through Michael addition between amine monomer and diarcrylate. The micelles of the pH-responsive polymers exhibited stability at physiological pH and accelerated doxorubicin (DOX) release without burst release in response to an acidic pH environment. Furthermore, N-(1-deoxylactitol-1-yl) dodecylamine (Gal-C12) as a targeting ligand was successfully bound to the micellar surface by hydrophobic interaction. The results of cellular uptake, in vitro cytotoxicity and cell cycle analysis indicated that the Gal functionalized micelles effectively transferred DOX to hepatoma cells (e.g. HepG2 cells) via asialoglycoprotein receptor (ASGPR) mediated endocytosis, released DOX from the micelles and resulted in enhanced proliferation inhibition efficacy. The ease of surface functionalization and enhanced drug efficacy make the present platform promising for hepatoma-targeted drug delivery in cancer therapy.