Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway.
Despite numerous applications, the cellular-clearance mechanism of multiwalled carbon nanotubes (MWCNTs) has not been clearly established yet. Previous in vitro studies showed the ability of oxidative enzymes to induce nanotube degradation. Interestingly, these enzymes have the common capacity to produce reactive oxygen species (ROS). Here, we combined material and life science approaches for revealing an intracellular way taken by macrophages to degrade carbon nanotubes. We report the in situ monitoring of ROS-mediated MWCNT degradation by liquid-cell transmission electron microscopy. Two degradation mechanisms induced by hydroxyl radicals were extracted from these unseen dynamic nanoscale investigations: a non-site-specific thinning process of the walls and a site-specific transversal drilling process on pre-existing defects of nanotubes. Remarkably, similar ROS-induced structural injuries were observed on MWCNTs after aging into macrophages from 1 to 7 days. Beside unraveling oxidative transformations of MWCNT structure, we elucidated an important, albeit not exclusive, biological pathway for MWCNT degradation in macrophages, involving NOX2 complex activation, superoxide production, and hydroxyl radical attack, which highlights the critical role of oxidative stress in cellular processing of MWCNTs.
Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS/Université Paris Diderot , Paris 75205, France.
Dan
D
Elgrabli
Laboratoire Matériaux et Phénomènes Quantiques, UMR7057 CNRS/Université Paris Diderot , Paris 75205, France.
Walid
W
Dachraoui
CNRS , Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.
Cécilia
C
Ménard-Moyon
Institut de Chimie et des Procédés pour L'Energie, l'Environnement et la Santé (ICPEES) UMR 7515, Université de Strasbourg , 25 rue Becquerel, 67087 Cedex 2 Strasbourg, France.
Xiao Jie
XJ
Liu
Institut de Chimie et des Procédés pour L'Energie, l'Environnement et la Santé (ICPEES) UMR 7515, Université de Strasbourg , 25 rue Becquerel, 67087 Cedex 2 Strasbourg, France.
Dominique
D
Bégin
Institut de Physique et Chimie de Strasbourg (IPCMS), UMR 7504 CNRS-Université de Strasbourg , 23 rue du Loess, BP 34, 67034 Cedex 2 Strasbourg, France.
Sylvie
S
Bégin-Colin
CNRS , Institut de Biologie Moléculaire et Cellulaire, Laboratoire d'Immunopathologie et Chimie Thérapeutique, 67000 Strasbourg, France.
Alberto
A
Bianco
Laboratoire Matière et Systèmes Complexes, UMR7057 CNRS/Université Paris Diderot , Paris 75205, France.
Florence
F
Gazeau
Laboratoire Matériaux et Phénomènes Quantiques, UMR7057 CNRS/Université Paris Diderot , Paris 75205, France.
Damien
D
Alloyeau
D000818:Animals; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000032:analysis* / Q000633:toxicity / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D008562:Membrane Glycoproteins; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
biodegradation; carbon nanotubes; genetic response; liquid-cell transmission electron microscopy; macrophages; reactive oxygen species