Citrate functionalized Mn3O4 in nanotherapy of hepatic fibrosis by oral administration

Aim: To test the potential of orally administered citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs) as a therapeutic agent against hepatic fibrosis and associated chronic liver diseases. Materials & methods: C-Mn3O4 NPs were synthesized and the pH dependent antioxidant mechanism was characterized by in vitro studies. CCl4 intoxicated mice were orally treated with C-Mn3O4 NPs to test its in vivo antioxidant and antifibrotic ability. Results: We demonstrated ultrahigh efficacy of the C-Mn3O4 NPs in treatment of chronic liver diseases such as hepatic fibrosis and cirrhosis in mice compared with conventional medicine silymarin without any toxicological implications. Conclusion: These findings may pave the way for practical clinical use of the NPs as safe medication of chronic liver diseases associated with fibrosis and cirrhosis in human subjects. Lay abstract: Hepatic fibrosis is a common response to chronic liver injury from a number of causes including alcohol, toxin, and persistent viral and helminthic infections, which may ultimately lead to hepatic carcinoma. Although billions of people are affected throughout the world, there is no drug available for treatment of this chronic disease. Here, in a preclinical study, we have shown that oral administration of citrate functionalized Mn3O4 nanoparticles can effectively reduce the extent of liver fibrosis in mice. We have also predicted the underlying therapeutic mechanism that involves mitochondria and antioxidant systems of the body. [GRAPHICS]