Hyaluronic Acid-Gold Nanoparticle/Interferon alpha Complex for Targeted Treatment of Hepatitis C Virus Infection

Abstract

Gold nanoparticles (AuNPs) have been extensively investigated as an emerging delivery-carrier of various biopharmaceuticals. Instead of nonspecific polyethylene glycol (PEG) conjugated interferon alpha (IFN alpha) for the clinical treatment of hepatitis C virus (HCV) Infection, in this work, a target-specific long-acting delivery system of IFN alpha was successfully developed using the hybrid materials of AuNP and hyaluronic add (HA). The HA-AuNP/IFN alpha complex was prepared by chemical binding of thiolated HA and physical binding of IFN alpha to AuNP. According to antiproliferation tests in Daudi cells, the HA-AuNP/IFN alpha complex showed a comparable biological activity to PEG-Intron with a highly enhanced stability in human serum. Even 7 days postinjection, HA-AuNP/IFN alpha complex was target-specifically delivered and remained in the murine liver tissue, whereas IFN alpha and PEG-Intron were not detected in the liver. Accordingly, HA-AuNP/IFN alpha complex significantly enhanced the expression of 2',5'-oligoadenylate synthetase 1 (OAS1) for innate immune responses to viral infection In the liver tissue, which was much higher than those by IFN alpha, PEG-Intron, and AuNP/IFN alpha complex. Taken together, the target specific HA-AuNP/IFN alpha complex was thought to be successfully applied to the systemic treatment of HCV infection.