초록 |
Toxic doses of acetaminophen(APAP) increase mitochondrial reactive oxygen species(ROS) and is the most common cause of acute hepatic failure in the U.S. Superoxide dismutase(SOD) and catalase(CAT) are the most important enzymes of the cell antioxidant defense system. However, in general, systemically delivering protein enzymes face several physiological barriers before reaching target tissue cells. To overcome these problems, we combine dopamine-conjugated hyaluronic acid(HA), a nontoxic hydrophilic natural polymer, with inorganic calcium phosphate(CAP) to form compact nanoparticles to deliver antioxidant enzymes. These particles improve liver cell-targeting and cellular uptake by receptor-mediated endocytosis and enable endosomal escape by CAP dissolution in acidic environment of endosome. Efficient cascade activity of SOD and CAT inside bio-hybrid nanoparticles is achieved in liver cells under oxidative stress. This would lead to improvement in APAP-induced liver injury. |