A carrier-free metal-organic hybrid nanoassembly with combination anti-viral and hepato-protective activity for hepatitis B treatment.

Abstract

Hepatitis B represents a major global public health burden, which is caused by the hepatitis B virus (HBV) with a high infection rate. Although several anti-HBV drugs have been developed for clinical treatment of hepatitis B, the current therapeutic strategies still suffer from undeniable adverse effects, insufficient efficacy after systemic administration and chronic inflammation. Here, we develop a carrier-free metal-organic hybrid nanoassembly that is co-loaded with tenofovir (TFV), an anti-viral agent and phosphorylated glycyrrhetinic acid (GAP), an anti-inflammatory compound (TFV/GAP/NA) to enhance the anti-HBV effect and alleviate the inflammatory response for hepatitis B treatment. The nanoassembly is easily prepared through the ionic interactions between the anionic phosphonate/phosphate groups from TFV/GAP and the zirconium cation, which has a stable nanostructure and a high drug-loading capacity. The nanoassembly prolongs the circulation time with reduced drug leakage in the blood and elevates drug accumulation in the liver after intravascular administration. After internalization mediated by the GAP ligand-GA receptor interaction, TFV/GAP/NA disassembles by the phosphatase-triggered degradation of the phosphate ester bonds in GAP and releases TFV, GAP and GA within the HBV-positive hepatocytes. The released TFV interferes with the HBV polymerase to inhibit the viral DNA replication, while the released GAP and GA suppress the pro-inflammatory protein expression. In mouse models, treatment with TFV/GAP/NA inhibits HBV production and alleviates inflammation-mediated liver injury.

• Authors: He Dong, Xiaodan Hong, Yingjiao He, Zhengxiang Bao, Ying Zhang, Shiyang Shen, Guangji Wang, Jingwei Zhang, Ran Mo
• Journal: Biomaterials science (Biomater Sci) Vol. 10 Issue 15 Pg. 4356-4366 (Jul 26 2022) ISSN: 2047-4849 [Electronic] England
• PMID: 35786722 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• DNA, Viral
• Organophosphates
• Phosphates
• Tenofovir
• Adenine

Topics

• Adenine (pharmacology)
• Animals
• Antiviral Agents (pharmacology)
• DNA Replication
• DNA, Viral (pharmacology, therapeutic use)
• Hepatitis B (drug therapy)
• Hepatitis B virus (metabolism)
• Inflammation (drug therapy)
• Mice
• Organophosphates
• Phosphates
• Tenofovir (pharmacology, therapeutic use)
• Virus Replication