Glucose-functionalized multidrug-conjugating nanoparticles based on amphiphilic terpolymer with enhanced anti-tumorous cell cytotoxicity

It is well known that combination therapy can significantly enhance the cytotoxicity and bypass some resistance mechanisms. However, the different solubility and pharmacokinetics of drugs limit the applications of combination therapy. In this study, novel glucose-functionalized polymeric micelle nanoparticles containing multidrugs were successfully fabricated and characterized. Two chemotherapeutic agents, cytarabine (Ara-C) and fluorodeoxyuridine (FUDR), were conjugated to a glucose-functionalized amphiphilic random terpolymer to create a novel nanocarrier for the delivery of multiple drugs simultaneously with an identical pharmacokinetic profile. The incorporation of d-glucose markedly increased the dispersity and biocompatibility of the novel polymeric micelles. In vitro drug release studies showed the two anticancer agents could be simultaneously released from multidrug-conjugating nanoparticles. Cellular uptake assay observed by confocal laser scanning microscopy and cytotoxicity tests performed by MTT assay against hepG2 human hepatoma cells indicated that glucose-functionalized multidrug-conjugating nanoparticles could be effectively internalized by HepG2 cells and showed much more effective growth-inhibitory activity than two single-drug-conjugating polymer aggregates or free drugs. This finding, therefore, illustrated that the d-glucose functionalized nanoparticles could be used as a novel potential multidrug delivery vehicle.