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Intracellular fate of carbon nanotubes inside murine macrophages: pH-dependent detachment of iron catalyst nanoparticles.

Cyrill Bussy 1 Erwan Paineau 2 Julien Cambedouzou 2, 3 Nathalie Brun 2 Claudie Mory 2 Barbara Fayard 2, 4 Murielle Salomé 4 Mathieu Pinault 5 Mickaël Huard 2 Esther Belade 6 Lucie Armand 6 Jorge Boczkowski 7 Pascale Launois 2 Sophie Lanone 8, *
* Corresponding author
1 INSERM U955, équipe 4
LPS - Laboratoire de Physique des Solides, Nanomedicine laboratory, IMRB - Institut Mondor de Recherche Biomédicale
7 INSERM U955, équipe 4
Service de Physiologie Explorations Fonctionnelles, Service de pneumologie et pathologie professionnelle, IMRB - Institut Mondor de Recherche Biomédicale
8 INSERM U955, équipe 4
Service de pneumologie et pathologie professionnelle, IMRB - Institut Mondor de Recherche Biomédicale
Abstract : BACKGROUND: Carbon nanotubes (CNT) are a family of materials featuring a large range of length, diameter, numbers of walls and, quite often metallic impurities coming from the catalyst used for their synthesis. They exhibit unique physical properties, which have already led to an extensive development of CNT for numerous applications. Because of this development and the resulting potential increase of human exposure, an important body of literature has been published with the aim to evaluate the health impact of CNT. However, despite evidences of uptake and long-term persistence of CNT within macrophages and the central role of those cells in the CNT-induced pulmonary inflammatory response, a limited amount of data is available so far on the CNT fate inside macrophages. Therefore, the overall aim of our study was to investigate the fate of pristine single walled CNT (SWCNT) after their internalization by macrophages. METHODS: To achieve our aim, we used a broad range of techniques that aimed at getting a comprehensive characterization of the SWCNT and their catalyst residues before and after exposure of murine macrophages: X-ray diffraction (XRD), High Resolution (HR) Transmission Electron Microscopy (TEM), High Angle Annular Dark Field-Scanning TEM (HAADF-STEM) coupled to Electron Energy Loss Spectroscopy (EELS), as well as micro-X-ray fluorescence mapping (μXRF), using synchrotron radiation. RESULTS: We showed 1) the rapid detachment of part of the iron nanoparticles initially attached to SWCNT which appeared as free iron nanoparticles in the cytoplasm and nucleus of CNT-exposed murine macrophages, and 2) that blockade of intracellular lysosomal acidification prevented iron nanoparticles detachment from CNT bundles and protected cells from CNT downstream toxicity. CONCLUSIONS: The present results, while obtained with pristine SWCNT, could likely be extended to other catalyst-containing nanomaterials and surely open new ways in the interpretation and understanding of CNT toxicity.
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https://www.hal.inserm.fr/inserm-00840223
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Submitted on : Tuesday, July 2, 2013 - 1:10:03 AM
Last modification on : Friday, October 23, 2020 - 4:59:13 PM
Long-term archiving on: : Thursday, October 3, 2013 - 4:07:30 AM

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Cyrill Bussy, Erwan Paineau, Julien Cambedouzou, Nathalie Brun, Claudie Mory, et al.. Intracellular fate of carbon nanotubes inside murine macrophages: pH-dependent detachment of iron catalyst nanoparticles.. Particle and Fibre Toxicology, BioMed Central, 2013, 10 (1), pp.24. ⟨10.1186/1743-8977-10-24⟩. ⟨inserm-00840223⟩

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