Early signs of multi-walled carbon nanotbues degradation in macrophages, via an intracellular pH-dependent biological mechanism; importance of length and functionalization.

Early signs of multi-walled carbon nanotbues degradation in macrophages, via an intracellular pH-dependent biological mechanism; importance of length and functionalization.
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DOI:
10.1186/s12989-016-0175-z
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发表时间:
2016-11-24
影响因子:
10
通讯作者:
Lanone S
Lanone S
中科院分区:
医学1区
文献类型:
--
作者:
Landry M;Pinault M;Tchankouo S;Charon É;Ridoux A;Boczkowski J;Mayne-L'Hermite M;Lanone S

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碳纳米管(CNT)与生物环境相互作用,参与其相关毒性。我们最近证明了pH是巨噬细胞内碳纳米管命运的重要参与者。我们想进一步表征这一过程,因此设计了一项研究,致力于破译巨噬细胞的碳纳米管生物降解,作为纳米毒理学方面的两个主要物理化学特性的功能;功能化的长度和程度。为了实现我们的目标,我们在一个单一的初始生产过程中合成了四种长度和/或表面化学性质不同的MWCNT: S-CNT(短),SF-CNT(短功能化),L-CNT(长)和LF-CNT(长功能化)。对暴露于RAW 264.7巨噬细胞6,24或48小时后恢复的碳纳米管进行拉曼光谱分析表明,随着时间的推移,碳纳米管在巨噬细胞内显示出生物降解的早期迹象。碳纳米管长度和功能化的调节,导致铁可及性的改变,都是生物降解过程的关键决定因素;短的原始碳纳米管比长碳纳米管(原始或功能化)更容易被生物降解,而短的功能化碳纳米管受到保护。用康那霉素孵育细胞完全阻止碳纳米管被修饰,表明这种生物降解过程依赖于细胞内ph依赖机制。有趣的是,尽管通过拉曼光谱有降解的证据,但碳纳米管的长度和直径在研究过程中没有改变。总之,我们的研究结果确定了巨噬细胞内碳纳米管生物降解的新机制。这可以为理解碳纳米管相关的毒性提供新的见解,并代表开发安全的(r)设计纳米材料的重要工具。本文的在线版本(doi:10.1186/s12989-016-0175-z)包含补充材料,可供授权用户使用。
Carbon nanotubes (CNT) can interact with the biological environment, which could participate in their associated toxicity. We recently demonstrated that pH is an important player of CNT fate inside macrophages. We wanted to further characterize such process, and therefore designed a study dedicated to decipher CNT biodegradation by macrophages, as a function of two major physico-chemical properties in regard with nanotoxicology; length and degree of functionalization. To achieve our aim, we synthesized, following a single initial production process, four MWCNT differing in length and/or surface chemistry: S-CNT (short), SF-CNT (short functionalized), L-CNT (long) and LF-CNT (long functionalized). Raman spectroscopy analysis performed on CNT recovered after exposure of RAW 264.7 macrophages for 6, 24, or 48 h demonstrate that CNT show early signs of biodegradation over time inside macrophages. The modulation of CNT length and functionalization, resulting in the modification of iron accessibility, both represent critical determinants of the biodegradation process; short pristine CNT were more prone to biodegradation than long CNT (pristine or functionalized), while short functionalized CNT were protected. Incubation of cells with Concanamycin completely prevents CNT from being modified, demonstrating that this biodegradation process is dependent on an intracellular pH-dependent mechanism. Interestingly, and despite evidence of degradation via Raman spectroscopy, the CNT length and diameter were not altered during the course of the study. In conclusion, our results identify a new mechanism of CNT biodegradation inside macrophages. This could give new insights for the understanding of CNT-associated toxicity, and represent important tools to develop safe(r)-by-design nanomaterials. The online version of this article (doi:10.1186/s12989-016-0175-z) contains supplementary material, which is available to authorized users.
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