Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery

Abstract

Our previous studies have successfully grafted biotin and galactose onto chitosan (CS) and synthesized biotin modified galactosylated chitosan (Bio-GC). The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1. At this N/P ratio, the transfection efficiency in the hepatoma cells was the highest with a slow release effect. Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation, and can target the transfection into hepatoma cells by combination with galactose and biotin receptors. The transfection rate was inhibited by the competition of galactose and biotin. Bio-GC nanomaterials were imported into cells’ cytoplasm by their receptors, followed by the imported exogenous gene transfected into the cells. Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice, by carrying the gene through the blood to the hepatoma tissue. Taken together, bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation, improving the rate of transfection in hepatoma cells, and transporting the gene into the cytoplasm in vitro and in vivo. Therefore, they are efficient hepatoma-targeting gene carriers.

Keywords

gene vector / hepatocellular carcinoma / nanoparticles / sustained release / gene therapy

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