Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

Abstract

Adriana Albini,1,* Arianna Pagani,2,3,* Laura Pulze,2 Antonino Bruno,3 Elisa Principi,3 Terenzio Congiu,4 Elisabetta Gini,2,4 Annalisa Grimaldi,2 Barbara Bassani,2,3 Silvio De Flora,5 Magda de Eguileor,2 Douglas M Noonan2,3 1Laboratory of Translational Research, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, 2Department of Biotechnologies and Life Sciences, University of Insubria, Varese, 3Scientific and Technology Park, IRCCS MultiMedica, Milano, 4Department of Surgical and Morphological Sciences, University of Insubria, Varese, 5Department of Health Sciences, University of Genoa, Genoa, Italy *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs. Keywords: nanoparticles, animal model, environmental exposure, inflammation, amyloid fibrils, macrophages