Hyaluronic Acid鈥揋old Nanoparticle/Interferon 伪 Complex for Targeted Treatment of Hepatitis C Virus Infection
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- 作者：Min-Young Lee ; Jeong-A Yang ; Ho Sang Jung ; Songeun Beack ; Jung Eun Choi ; Wonhee Hur ; Heebeom Koo ; Kwangmeyung Kim ; Seung Kew Yoon ; Sei Kwang Hahn
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：November 27, 2012
- 年：2012
- 卷：6
- 期：11
- 页码：9522-9531
- 全文大小：670K
- 年卷期：v.6,no.11(November 27, 2012)
- ISSN：1936-086X
文摘
Gold nanoparticles (AuNPs) have been extensively investigated as an emerging delivery carrier of various biopharmaceuticals. Instead of nonspecific polyethylene glycol (PEG) conjugated interferon 伪 (IFN伪) for the clinical treatment of hepatitis C virus (HCV) infection, in this work, a target-specific long-acting delivery system of IFN伪 was successfully developed using the hybrid materials of AuNP and hyaluronic acid (HA). The HA鈥揂uNP/IFN伪 complex was prepared by chemical binding of thiolated HA and physical binding of IFN伪 to AuNP. According to antiproliferation tests in Daudi cells, the HA鈥揂uNP/IFN伪 complex showed a comparable biological activity to PEG-Intron with a highly enhanced stability in human serum. Even 7 days postinjection, HA鈥揂uNP/IFN伪 complex was target-specifically delivered and remained in the murine liver tissue, whereas IFN伪 and PEG-Intron were not detected in the liver. Accordingly, HA鈥揂uNP/IFN伪 complex significantly enhanced the expression of 2鈥?5鈥?oligoadenylate synthetase 1 (OAS1) for innate immune responses to viral infection in the liver tissue, which was much higher than those by IFN伪, PEG-Intron, and AuNP/IFN伪 complex. Taken together, the target-specific HA鈥揂uNP/IFN伪 complex was thought to be successfully applied to the systemic treatment of HCV infection.