Multifunctional self-assembled micelles of galactosamine-hyaluronic acid-vitamin E succinate for targeting delivery of norcantharidin to hepatic carcinoma. (1st October 2018)

• Record Type: Journal Article
• Authors: Jiang, Shulong; Li, Mengying; Hu, Ying; Zhang, Zhenhai; Lv, Huixia
• Is Part Of: Carbohydrate polymers. Volume 197(2018)
• Page Start: 194
• Page End: 203
• Publication Date: 2018-10-01
• Subjects: Norcantharidin -- Hyaluronic acid -- Galactosamine -- Micelles -- Hepatocellular carcinoma; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2018.05.090
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: A novel liver-targeting drug delivery system was developed. Gal-HA-VES has the same action of TPGS as a P -glycoprotein inhibitor. NCTD/Gal-HA-VES exhibited enhanced antitumor activity with lower systemic toxicity. NCTD/Gal-HA-VES exert synergistic anti-tumor effect of VES. 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.