Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway
Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway
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DOI：
10.1021/acsnano.5b03708
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发表时间：
2015-10-01
期刊：
影响因子：
17.1
通讯作者：
Alloyeau, Damien
中科院分区：
文献类型：
--
作者：
Elgrabli, Dan;Dachraoui, Walid;Alloyeau, Damien
尽管应用广泛，但多壁碳纳米管（MWCNT）的细胞清除机制尚未明确。先前的体外研究表明氧化酶具有诱导纳米管降解的能力。有趣的是，这些酶具有产生活性氧（ROS）的共同能力。在这里，我们结合了材料和生命科学方法，揭示了巨噬细胞降解碳纳米管的细胞内方式。我们报告了通过液体细胞透射电子显微镜对 ROS 介导的 MWCNT 降解进行原位监测。从这些看不见的动态纳米级研究中提取了羟基自由基引起的两种降解机制：壁的非位点特异性减薄过程和纳米管预先存在的缺陷的位点特异性横向钻孔过程。值得注意的是，在老化为巨噬细胞 1 至 7 天后，在 MWCNT 上观察到类似的 ROS 诱导的结构损伤。除了揭示多壁碳纳米管结构的氧化转化之外，我们还阐明了巨噬细胞中多壁碳纳米管降解的一个重要但并非唯一的生物途径，包括NOX2复合物激活、超氧化物产生和羟基自由基攻击，这凸显了氧化应激在多壁碳纳米管细胞加工中的关键作用。
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.