Silver Nanoparticle Based Codelivery of Oseltamivir to Inhibit the Activity of the H1N1 Influenza Virus through ROS-Mediated Signaling Pathways

As the therapeutic agent for antiviral applications, the clinical use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention in recent ye...

Full description

Saved in:
Bibliographic Details
Published in:ACS applied materials & interfaces 2016-09, Vol.8 (37), p.24385-24393
Main Authors: Li, Yinghua, Lin, Zhengfang, Zhao, Mingqi, Xu, Tiantian, Wang, Changbing, Hua, Liang, Wang, Hanzhong, Xia, Huimin, Zhu, Bing
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents
Dogs
Drug Resistance, Viral
Humans
Influenza A Virus, H1N1 Subtype
Metal Nanoparticles
Oseltamivir
Reactive Oxygen Species
Silver
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As the therapeutic agent for antiviral applications, the clinical use of oseltamivir is limited with the appearance of drug-resistant viruses. It is important to explore novel anti-influenza drugs. The antiviral activity of silver nanoparticles (AgNPs) has attracted increasing attention in recent years and was a possibility to be employed as a biomedical intervention. Herein, we describe the synthesis of surface decoration of AgNPs by using oseltamivir (OTV) with antiviral properties and inhibition of drug resistance. Compared to silver and oseltamivir, oseltamivir-modified AgNPs (Ag@OTV) have remarkable inhibition against H1N1 infection, and less toxicity was found for MDCK cells by controlled-potential electrolysis (CPE), MTT, and transmission electron microscopy (TEM). Furthermore, Ag@OTV inhibited the activity of neuraminidase (NA) and hemagglutinin (HA) and then prevented the attachment of the H1N1 influenza virus to host cells. The investigations of the mechanism revealed that Ag@OTV could block H1N1 from infecting MDCK cells and prevent DNA fragmentation, chromatin condensation, and the activity of caspase-3. Ag@OTV remarkably inhibited the accumulation of reactive oxygen species (ROS) by the H1N1 virus and activation of AKT and p53 phosphorylation. Silver nanoparticle based codelivery of oseltamivir inhibits the activity of the H1N1 influenza virus through ROS-mediated signaling pathways. These findings demonstrate that Ag@OTV is a novel promising efficient virucide for H1N1.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.6b06613