Abstract

Noroviruses (NoV) have enhanced tropism for the gastrointestinal (GI) tract and are the major cause of nonbacterial gastroenteritis in humans. Titanium dioxide (TiO2) nanoparticles (NPs) used as food additives, dietary supplements, and cosmetics accumulate in the GI tract. We investigated the effect anatase TiO2 NPs on NoV replication and host response during virus infection, using murine norovirus (MNV-1) infection of RAW 264.7 macrophages. Pretreatment with 20 μg/ml anatase NPs significantly reduced the viability of macrophages alone or during virus infection, but did not alter virus replication. In contrast, pre-incubation with 2 μg/ml anatase NPs reduced virus replication fivefold at 48 h. The presence of anatase NPs during MNV-1 infection evoked a pro-inflammatory response, as measured by a significant increase in expression of cytokines, including IL-6, IFN-γ, TNFα and the TGFβ1. No genotoxic insults due to anatase TiO2 NPs alone or to their presence during MNV-1 infection were detected. This study highlights important safety considerations related to NP exposure of the GI tract in individuals infected with noroviruses or other foodborne viruses.

Highlights

  • Nanomedicine has evolved into a discipline with high impact and potential in the fields of infectious disease therapeutics, vaccine delivery systems, and cancer therapeutics, among others [1,2,3,4,5]

  • We present evidence that while pre-incubation with TiO2 NPs has inert effects on virus replication, they do not lead to genotoxic damage, but do, promote differential modulation of the host response and toxicity on the host cells

  • We dosed the macrophages at two concentrations, 20 μg/ml and 2 μg/ml of Anatase NPs, and analyzed viability and morphology of RAW cells

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Summary

Introduction

Nanomedicine has evolved into a discipline with high impact and potential in the fields of infectious disease therapeutics, vaccine delivery systems, and cancer therapeutics, among others [1,2,3,4,5]. A variety of nanomaterials, including polymeric NPs, polymeric micelles, graphite, silver, gold, silica, carbon nanotubes and polylactide-coglycolides (PLGA) are being used as drug delivery vehicles or as adjuvants for vaccines [6]. There has been increased use of a variety of NPs in consumer products [9, 10], with over 1500 products currently used in several sectors, including foods, beverages, cosmetics and home appliances [11, 12]. TiO2 NPs are widely used in pharmaceuticals, cosmetics and food products [13, 14]. They are employed as a pigment to provide whiteness and opacity to paints, coatings, plastics, papers, inks, food products, pills, tablets and toothpastes [15]. The use of TiO2 as food additive results in an estimated dietary consumption of Volume 1 Issue 3, December 2016

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