Intracellular degradation of functionalized carbon nanotube/iron oxide hybrids is modulated by iron via Nrf2 pathway

Dan Elgrabli,Damien Alloyeau,Cécilia Ménard-Moyon,Alberto Bianco,Dominique Bégin,Florence Gazeau,Sylvie Bégin-Colin,Hélène De Marmier,Walid Dachraoui

doi:10.1038/srep40997

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 NOX2 complex activation and O2•−, H2O2 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.

Highlights

The unique properties of carbon nanotubes (CNTs) have allowed the exploration of a plethora of applications in various fields, such as electronics, energy storage and conversion, sensors, automotive and nanomedicine[1,2,3,4,5]
NAC significantly reduced the degradation speed of MWCNTs from 0.9%/h to 0.3%/h, but slightly reduced the degradation speed of Fe@MWCNTs from 0.3%/h to 0.2%/h (Fig. 1B) between 24 and 48 h. These results suggest either a difference in the production of reactive oxygen species (ROS) triggered by MWCNTs compared to Fe@MWCNTs or some role of iron oxide NPs in the degradation mechanism
ROS induced by MWCNTs or Fe@MWCNTs in the presence or absence of NAC were quantified by 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA)

Summary

Introduction

The unique properties of carbon nanotubes (CNTs) have allowed the exploration of a plethora of applications in various fields, such as electronics, energy storage and conversion, sensors, automotive and nanomedicine[1,2,3,4,5]. Associating CNTs with metal oxide nanoparticles (NPs) is an even more promising approach since the properties of each material can be combined advantageously. While CNTs exhibit outstanding electrical and thermal conductivities, mechanical properties and high specific surface area, magnetic iron oxide nanoparticles have shown great promises for biotechnology, sensing, data storage as well as imaging and therapeutic applications. The long term fate and biodegradability in the body of CNTs and metal oxide/CNT hybrids is still a subject of debate that considerably slows their development and raises serious health issues. Based on potential asbestos-like pathogenicity, the long term fate of anisotropic carbon materials raises specific concerns related to their architecture[7]. Some CNTs have been associated with iron oxide nanoparticles for biomedical applications combining magnetic resonance imaging, hyperthermia therapy, and magnetic manipulation[10,11,12,13]. We reveal that ROS-induced MWCNT degradation can be modulated by exogenous sources of iron through Nrf[2] pathway

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