Hyaluronic Acid-Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection
- Hyaluronic Acid-Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection
- Min-Young Lee; Jeong-A Yang; Ho Sang Jung; Songeun Beack; Jung Eun Choi; Wonhee Hur; 구희범; 김광명; Seung Kew Yoon; Sei Kwang Hahn
- gold nanoparticle; hyaluronic acid; interferon α; targeted delivery
- Issue Date
- ACS Nano
- VOL 6, NO 11, 9522-9531
- Gold nanoparticles (AuNPs) have been extensively investigated as an emerging delivery carrier of various biopharmaceuticals. Instead of nonspecific polyethylene glycol (PEG) conjugated interferon α (IFNα) for the clinical treatment of hepatitis C virus (HCV) infection, in this work, a target-specific long-acting delivery system of IFNα was successfully developed using the hybrid materials of AuNP and hyaluronic acid (HA). The HA–AuNP/IFNα complex was prepared by chemical binding of thiolated HA and physical binding of IFNα to AuNP. According to antiproliferation tests in Daudi cells, the HA–AuNP/IFNα complex showed a comparable biological activity to PEG-Intron with a highly enhanced stability in human serum. Even 7 days postinjection, HA–AuNP/IFNα complex was target-specifically delivered and remained in the murine liver tissue, whereas IFNα and PEG-Intron were not detected in the liver. Accordingly, HA–AuNP/IFNα 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 IFNα, PEG-Intron, and AuNP/IFNα complex. Taken together, the target-specific HA–AuNP/IFNα complex was thought to be successfully applied to the systemic treatment of HCV infection.
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