title: Intracellular degradation of functionalized carbon nanotube/iron oxide hybrids is modulated by iron via Nrf2 pathway.
abstract: The in vivo fate and biodegradability of carbon nanotubes is still a matter of debate despite tremendous applications. In this paper we describe a molecular pathway by which macrophages degrade functionalized multi-walled carbon nanotubes (CNTs) designed for biomedical applications and containing, or not, iron oxide nanoparticles in their inner cavity. Electron microscopy and Raman spectroscopy show that intracellularly-induced structural damages appear more rapidly for iron-free CNTs in comparison to iron-loaded ones, suggesting a role of iron in the degradation mechanism. By comparing the molecular responses of macrophages derived from THP1 monocytes to both types of CNTs, we highlight a molecular mechanism regulated by Nrf2/Bach1 signaling pathways to induce CNT degradation via NOX2complex activation and O2•-, H2O2and OH•production. CNT exposure activates an oxidative stress-dependent production of iron via Nrf2 nuclear translocation, Ferritin H and Heme oxygenase 1 translation. Conversely, Bach1 was translocated to the nucleus of cells exposed to iron-loaded CNTs to recycle embedded iron. Our results provide new information on the role of oxidative stress, iron metabolism and Nrf2-mediated host defence for regulating CNT fate in macrophages.
authors.affiliation: Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS/Université Paris Diderot, 75013 Paris, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Elgrabli
authors.affiliation: Laboratoire Matériaux et Phénomènes Quantiques, UMR7057 CNRS/Université Paris Diderot, 75013 Paris, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Dachraoui
authors.affiliation: Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS/Université Paris Diderot, 75013 Paris, France.
authors.forename: Hélène de
authors.initials: H
authors.lastname: Marmier
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Ménard-Moyon
authors.affiliation: Institut de Chimie et des Procédés pour L'Energie, l'Environnement et la Santé (ICPEES) UMR 7515, Université de Strasbourg, 25 rue Becquerel, 67087 Strasbourg cedex 2, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bégin
authors.affiliation: Institut de Physique et de Chimie de Strasbourg (IPCMS) UMR 7504 CNRS-Université de Strasbourg, 23 rue du Loess, BP 34, 67034 Strasbourg cedex 2, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bégin-Colin
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Laboratoire Matériaux et Phénomènes Quantiques, UMR7057 CNRS/Université Paris Diderot, 75013 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Alloyeau
authors.affiliation: Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS/Université Paris Diderot, 75013 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Gazeau