Redox-responsive chitosan oligosaccharide-SS-Octadecylamine polymeric carrier for efficient anti-Hepatitis B Virus gene therapy

Abstract

DrzBC and DrzBS (10-23 DNAzyme) could block the expression of HBV e- and s- gene respectively. But the application of 10-23 DNAzyme was limited owing to the lack of appropriate delivery vehicles. Chitosan oligosaccharide-SS-Octadecylamine (CSSO), a redox-responsive nano-sized polymeric carrier, could self-aggregate and bind with DNA by electrostatic interaction at proper mass ratio. Compared with the traditional commercial carrier Lipo2000, CSSO exhibited lower cytotoxicity, efficient cellular uptake by targeting cells, and rapidly DNA released in cytoplasm after escaping from endosomes. Including the same DNA concentration, Lipo2000/(DrzBC or DrzBS) showed maximum inhibitory rate on HBeAg (47.29 ± 1.86%) and HBsAg (33.58 ± 0.72%) secretion after 48 h incubation, and then both decreased. In contrast, HBeAg secretion inhibition by CSSO/DrzBC and HBsAg secretion inhibition by CSSO/DrzBS were up to 73.86 ± 1.77% and 67.80 ± 2.51% at 48 h, and further increased to 83.83 ± 2.34% and 76.79 ± 2.18% at 72 h, respectively. CSSO is a promising redox-responsive polymeric carrier for efficient anti-Hepatitis B Virus gene therapy.

Keywords: 10–23DNAzyme; Anti-Hepatitis B Virus; Chitosan oligosaccharide-SS-Octadecylamine; Gene therapy; Redox-responsive.