Impact and translocation of titanium dioxide nanoparticles (TiO2-NPs) on gastro-intestinal models

As nanosciences and nanotechnologies develop, nanoparticles (NP) are introduced in a wider range of daily-used products. Titanium dioxide particles are among the most produced mineral particles in the world; they are included in the composition of many products and among them food products. TiO2 is an authorized food additive (in Europe E171) primarily used for its white color. This food additive is mainly composed of particles with diameter >100 nm, but a recent study and our own unpublished data show that 35-40% of these particles are less than 100 nm in diameter, i.e. are nanoparticles (Weir et al., 2012).

As they are present in food products, these TiO2-NPs are ingested, and daily consumption of TiO2 from food has been estimated to be in the range of 0.2-2 mg TiO2 per kg of body weight and per day (Weir et al., 2012). As a consequence the function of gastro-intestinal epithelium may be altered, and particles – potentially nanoparticles- may translocate from the intestinal lumen to internal tissues.

 

Our work aims at identifying NP impact and translocation through the gut, by using in vitro gut models that reproduce different parts of the gastro-intestinal system. These in vitro mono- or co-cultures are grown on semi-permeable inserts, and exposed to NPs on their apical side. NP cyto- and genotoxicity is assessed, together with the oxidative stress generated in cells by NP accumulation. Modulation of protein expression in NP-exposed cells is identified, suggesting interesting mechanistic outcomes such as impairment of paracellular permeability by TiO2-NPs (Brun et al., 2014).

To assess NP translocation, in vitro on these cell models, the originality of our work is that we use techniques that are proposed on medium- or large-scale facilities, i.e. nuclear microprobes and synchrotrons. Particle-induced X-ray emission (PIXE), couples to Rutherford backscattering (RBS) is used to image Ti distribution and to locally measure Ti content in TiO2-NP exposed cells. Micro-X-ray fluorescence (µXRF) is also used to image Ti distribution, with a higher spatial resolution. This technique is not quantitative but its advantage is that it can be coupled, on some synchrotron beamlines, to in situ chemical analysis by X-ray absorption spectroscopy (XAS, i.e. XANES and EXAFS). For the best spatial resolution, we use transmission electron microscopy (TEM) and scanning-transmission electron microscopy (STEM). Using this combination of techniques, we showed that TiO2-NPs translocated through an in vitro model of M-cells, but not through the regular epithelium lining the ileum (Brun et al., 2014). Translocation and intracellular sequestration did not lead to NP dissolution (Veronesi et al., 2012).

 

This project is supported by the labex SERENADE; it was funded by INERIS and French research ministry via the post-Grenelle de l’environnement program (NanoTRANS project), then by the Ile de France region via the C’Nano framework (NanoDIG project). It is currently funded by ANSES (Nanogut project).

 

References :

E. Brun, G. Veronesi, F. Barreau, C. Chanéac, B. Fayard, S. Sorieul, A. Mabondzo, N. Herlin-Boime, M. Carrière. Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia. Particle and Fibre Toxicology, in press, 2014.

 

G. Veronesi, E. Brun, B. Fayard, M. Cotte, M. Carrière. Structural properties of rutile TiO2 nanoparticles accumulated in a model of gastrointestinal epithelium elucidated by micro-beam X-ray Absorption Fine Structure spectroscopy. Appl Phys Lett, 100(21), 2012.

 

Maj : 27/03/2014 (906)

 

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