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ACS Nano. 2012 Nov 27;6(11):9522-31. doi: 10.1021/nn302538y. Epub 2012 Oct 26.

Hyaluronic acid-gold nanoparticle/interferon α complex for targeted treatment of hepatitis C virus infection.

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1
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea.

Abstract

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.

PMID:
23092111
DOI:
10.1021/nn302538y
[Indexed for MEDLINE]

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