Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells

Abstract

Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al₂O₃ nanoparticles, while AlCl₃ showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 µg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.

KEYWORDS:

• Nanoparticles
• aluminum
• gastrointestinal tract
• microarray
• toxicology

Acknowledgments

The authors are grateful to the MRic-TEM core facility of BIOSIT (CNRS-INSERM UMS 3480, US_S 018, University of Rennes 1, France) for the transmission electronic microscopy. We would like to thank Rachelle Lanceleur for technical assistance in TEM uptake experiments.

Availability of data and material

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This publication, as part of the German-French SolNanoTOX project was funded by the German Research Foundation DFG (Grant Numbers LA 3411/1-1), by the French ‘Agence Nationale de la Recherche’ ANR (Project ID ANR-13-IS10-0005).