Promising positive liver targeting delivery system based on arabinogalactan-anchored polymeric micelles of norcantharidin.

Liver cancer is the third most common cause of global cancer-related deaths. This study focused on newly developed drug delivery systems with hepatocyte asialoglycoprotein receptor binding targeting the liver. Although norcantharidin (NCTD) is effective in primary liver cancer treatment, its toxicity in the urinary system remains. Positive liver-targeting effect could be achieved by preparing polymer micelles by arabinogalactan on the surface of N-(4-methylimidazole)-hydroxyethyl-chitosan (MHC). HepG2 cells were used to analyze the cytotoxicity, invasion, apoptosis and uptake of NCTD-loaded micelles. The in vivo antitumor efficacy of NCTD-M was evaluated using tumor-bearing nude mice. Successful preparation of NCTD-M was shown. In vivo imaging showed that micelles significantly increased positive liver drug targeting. Laser confocal microscopy showed increased cellular uptake of micelles. NCTD-M also enhanced cell invasion and the proportion of apoptotic cells. Compared with the other groups, the micelles showed better antitumor effects in vivo. Therefore, the positive liver-targeting NCTD-M, which can enhance antitumor efficacy and reduce toxicity, could be a promising and effective therapeutic agent for liver cancer treatment.