Target delivery of small interfering RNAs with vitamin E- loaded lipid nanoparticles in inhibition of hepatitis C virus core protein expression in mouse model
10.3760/cma.j.issn.1007-3418.2018.05.013
- VernacularTitle: 小鼠模型中维生素E脂质体纳米颗粒靶向转运siRNA抑制丙型肝炎病毒核心蛋白表达
- Author:
Yuanyuan YE
1
;
Hong CHEN
1
;
Yan YAN
1
;
Weixian CHEN
1
;
Ying HUANG
2
Author Information
1. Department of Laboratory, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
2. Department of Infectious Disease, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
- Publication Type:Journal Article
- Keywords:
Hepatitis C virus;
RNA interference;
Vitamin E;
Nano paticle;
Targeted therapy
- From:
Chinese Journal of Hepatology
2018;26(5):382-387
- CountryChina
- Language:Chinese
-
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.
