The human body is increasingly exposed to nanoscale materials that are widely developed for industrial use or for biomedical applications. Moreover, these engineered nano-objects are not the only worrying source of exposure for humans, since anthropogenic nanomaterials released in the environments also constitute a growing threat to public health. Therefore, addressing the risks associated to nanomaterials is a complex and sensitive societal issue which requires identifying all the nano-objects to which humans are exposed and understanding their lifecycle in the organism.  Here, we reveal for the first time an entry pathway for multi-wall carbon nanotubes (MWCNTs) found in air pollution to the airways of Parisian children [1]. Given the key role of macrophages in the process of foreign substances, we have also exploited multidisciplinary know-how in materials and life sciences to unravel the way taken by these cells to degrade MWCNTs [2].

We used high-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy to show the presence of MWCNTs in broncho-alveolar lavage-fluids (fig 1a) and inside lung cells (fig 1b) of asthmatic children. These CNTs are present in all examined samples (n = 64) and they are similar to those found in dusts and vehicle exhausts (fig 1c) collected in Paris and other parts of the world (USA, India…). These results strongly suggest that humans are routinely exposed to MWCNTs and demonstrate that advanced atomic-scale characterizations are essential to identify ultrafine particles in the environment or in the organism [1].

Like most nanomaterials, the “journey” of MWCNTs in the organism mainly ends in macrophages of lung after inhalation, or of liver and spleen after intravenous injection. In order to consider the reciprocity of the interactions between MWCNTs and macrophages, we have simultaneously examined the influences of intracellular environment on the atomic structure of nanomaterials and the biologic response of the cells to MWCNTs. Gene and protein expression profiles of macrophages exposed to MWCNTs allowed identifying the formation of reactive oxygen species (ROS) as a non-ambiguous causal process for triggering intracellular degradation of MWCNTs. Consistent with cellular approach, we could monitor with unprecedented nanoscale resolution the ROS-induced damages in MWCNTs using transmission electron microscopy in liquid (fig 2). Remarkably, we demonstrate that this in situ imaging of MWCNT degradation recapitulates the long term ROS-induced aging of MWCNT in macrophages and reveals the structural mechanisms of MWCNT transformation over time. More generally, such dynamical observations of nanomaterials under oxidative stress is a step forward for studying their behavior and reactivity in biological environment at the relevant scale. These mechanistic insights on the biological responses to nanomaterial exposure and the resulting nanomaterial transformations are of primary importance for both material scientists interested in optimizing the reactivity of nanostructures in biological environment and biologists anxious to evaluate the effects and potential risk of nanomaterials for the organism [2].

References:

[1] Jelena Kolosnjaj-Tabi et al, Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children, EBioMedicine 2 (2015), p. 3988.

[2] Dan Elgrabli et al. Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway, ACS Nano 9 (2015), p. 10113.

Figures:

Fig 1: TEM images of (a) broncho-alveolar lavage-fluids and (b) macrophages cells, both extracted from the lungs of asthmatic Parisian children. (c) Particulate matter extracted from vehicle exhausts. Carbon nanospherules (black arrows) and MWCNT structures (red arrows) are observed in all the samples. In insert of 1a: HRTEM image revealing interlayer spacings characteristic of graphitic structures.

Fig 2: In situ STEM imaging in water showing the oxidative degradation of a MWCNT filled with iron-oxide nanoparticles induced by ROS produced by radiolysis (the acquisition time is indicated on each image). White arrows show the tearing of the nanotube along the interface between the graphitic structure and the iron oxide nanoparticles inserted in the carbon walls.

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