Abstract
A polymer of Galactosamine-hyaluronic acid-Vitamin E succinate (Gal-HA-VES) was designed to prepare multifunctional self-assembled micelles for delivery of Norcantharidin (NCTD) to Hepatic carcinoma. NCTD/Gal-HA-VES showed higher cytotoxicity toward CD44-overexpressing MCF-7 cells, MCF-7/Adr cells and ASGP-R overexpressing HepG2 cells, consistent with the enhanced cellular uptake in the selected cell models, indicating Gal-HA-VES micelles were taken up in MCF-7 and HepG2 cells by CD44 and ASGPR receptor mediated endocytosis, respectively. Moreover, the accumulation of Rhodamine 123 demonstrated that Gal-HA-VES has the same action of TPGS as a P-glycoprotein inhibitor blocked drug efflux-related MDR mechanism in resistant MCF-7/Adr cells. The Cell apoptosis assays indicated that NCTD/Gal-HA-VES were more effective in triggering apoptosis, compared with free NCTD or NCTD/HA-VES groups. In vivo study demonstrated that NCTD/Gal-HA-VES group exhibited enhanced tumor targeting and antitumor activity with lower systemic toxicity. Hence NCTD/Gal-HA-VES micelles system can achieve significant tumor targeting and effective treatment of hepatic carcinoma.
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