Intracellular degradation of functionalized carbon nanotube-iron oxide hybrids is modulated by iron via Nrf2 pathwayReport as inadecuate




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1 MSC - Matière et Systèmes Complexes 2 MPQ - Laboratoire Matériaux et Phénomènes Quantiques 3 IBMC - Institut de biologie moléculaire et cellulaire 4 ICPEES - Institut de chimie et procédés pour l-énergie, l-environnement et la santé 5 IPCMS - Institut de Physique et Chimie des Matériaux de Strasbourg

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 NOX 2 complex activation and O 2 • − , H 2 O 2 and 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.





Author: Dan Elgrabli - Walid Dachraoui - Hélène De Marmier - Cécilia Ménard-Moyon - Dominique Bégin - Sylvie Bégin-Colin - Alberto

Source: https://hal.archives-ouvertes.fr/



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