期刊
CARBOHYDRATE POLYMERS
卷 212, 期 -, 页码 215-221出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2019.02.047
关键词
Chitosan oligosaccharide-SS-Octadecylamine; Redox-responsive; 10-23DNAzyme; Anti-Hepatitis B Virus; Gene therapy
资金
- Zhejiang provincial natural science foundation-Qing Shan Hu Science & Technology City Union Foundation [LQY19H300001]
- National Nature Science Foundation of China [81402862]
- hospital pharmacy special research project of Zhejiang Pharmaceutical Association [2018ZYY02]
- Zhejiang provincial natural science foundation [LQ15H280005]
- Zhejiang Traditional Chinese Medicine Science and Technology Program [2016ZA116]
- Zhejiang Medical Technology Program [2017178266]
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.
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