Hepatocyte-targeting and microenvironmentally responsive glycolipid-like polymer micelles for gene therapy of hepatitis B
Brief intro:
- Author: Jing Miao, Xiqin Yang, Xuwei Shang, Zhe Gao, Qian Li, Yun Hong, Jiaying Wu, Tingting Meng, Hong Yuan, and Fuqiang Hu
- Journal: Mol Ther Nucleic Acids
- Doi: https://www.doi.org/10.1016/j.omtn.2021.02.013
- Publication Date: 2021 Feb 18
Products/Services used in the paper
Quotation shows PackGene:rAAV8- 1.3HBV (1 x10^11 Viral genome, vg) was purchased from PackGene Biotech and used to obtain HBV- infected animal models.
Research Field:liver
AAV Serotype:AAV8
Targeted organ:liver
Animal or cell line strain:Male BALB/c (6–8 weeks) mice
Abstract
Hepatitis B (HB) is a viral infectious disease that seriously endangers human health, and since there are no radical drugs to counter this, effective and safe therapies urgently need to be developed. HB virus (HBV) mainly infects hepatocytes (HCs), while the drugs are easily phagocytosed by Kupffer cells (KCs). In this study, the glutathione concentration difference between HCs and KCs was examined and utilized in an ideal drug-release strategy. Here, galactosylated chitosan-oligosaccharide-SS-octadecylamine (Gal-CSSO) was prepared to accurately deliver 10-23 DNAzyme DrzBC (blocking HBeAg expression) or DrzBS (blocking HBsAg expression) in targeted HB therapy. In vitro Gal-CSSO systems exhibited low cytotoxicity, endosomal escape, and glutathione responsiveness. The HBeAg and HBsAg secretion of HepG2.2.15 was significantly decreased by Gal-CSSO systems, and the maximum inhibition rates were 1.82-fold and 2.38-fold greater than those of commercial Lipofectamine 2000 (Lipo2000) systems. In vivo Gal-CSSO systems exhibited HC targeting and HC microenvironmental responsiveness without noticeable hepatotoxicity or systemic toxicity. The HBeAg and HBsAg titers of the HBV-infected mice were evidently decreased by Gal-CSSO systems, and the inhibition rates were 1.52-fold and 1.22-fold greater than those of Lipo2000 systems. This study presents a kind of glycolipid-like polymer micelles that promise efficient and safe gene therapy of HB.
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