Target delivery of small interfering RNAs with vitamin E- loaded lipid nanoparticles in inhibition of hepatitis C virus core protein expression in mouse model / 中华肝脏病杂志

ABSTRACT

Objective@#To study the efficacy of vitamin E-loaded lipid nanoparticles (VE-DC) in the mouse model to target small interfering RNA (siRNA) for inhibition of hepatitis C virus(HCV) core protein expression. @*Methods@#A high-pressure hydrodynamic method was adopted to construct an animal model of liver-specific expression to inject the plasmid containing HCV core protein into mice tail vein. Western blotting and immunofluorescence techniques were used to evaluote the liver targeting property of VE - DC/siRNA nanoparticles and the effectiveness to repress HCV Core expression. Dual luciferase reporter gene assays and in vivo imaging in mice further confirmed the inhibiting effect of VE-DC/siRNA on gene expression mediated by HCV 5' untranslated region. The adverse reactions of VE-DC/siRNA were reported by detecting serum creatinine, white blood cells and interferon. Student’s t - test and one -way analysis of variance were used to compare the difference between the two groups, and P < 0.05 was considered statically significant. @*Results@#The dual luciferase reporter gene analysis showed that the luciferase activity of the VE-DC/siRNA treated group was 39.67 ± 15.53, which was significantly lower than 77.33±11.06 of the DC/siRNA group and 91.67 ± 13.65 of the siRNA treated group, P < 0.05. The difference was statistically significant, and there was no obvious organ toxicity and obvious immune response to VE-DC/siRNA. Nanoparticle VE-DC has a good liver targeting ability, which can transport siRNA to the liver and effectively inhibit the expression of HCV Core, with an average inhibition rate of 83.01%. @*Conclusion@#VE-DC could target the delivery of siRNA to the liver and inhibit the expression of HCV- related genes in a mouse model, showing high effectiveness and low toxicity.