Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress
Metabolomics of silver nanoparticles toxicity in HaCaT cells: structure-activity relationships and role of ionic silver and oxidative stress
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DOI：
10.1080/17435390.2016.1177744
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发表时间：
2016-01-01
期刊：
影响因子：
5
通讯作者：
Duarte, Iola F.
中科院分区：
文献类型：
--
作者：
Carrola, Joana;Bastos, Veronica;Duarte, Iola F.
随着银纳米粒子的广泛使用，人们越来越关注其对人类健康的潜在风险，因此需要更多地了解其生物效应。这项工作的目的是系统地研究细胞代谢的变化在多大程度上取决于AgNPs的性质，使用核磁共振代谢组学。将人皮肤角质形成细胞（HaCaT细胞）暴露于10、30或60nm直径的柠檬酸盐包被的AgNPs和30nm包被柠檬酸盐（CIT）、聚乙二醇（PEG）或牛血清白蛋白（BSA）的AgNPs中，以评估NP大小和表面化学的影响。总体而言，cit包被的60nm和peg包被的30nm AgNPs对细胞活力和代谢的影响最小。此外，还研究了离子银和活性氧（ROS）介导的作用，并与cit包覆的30nm颗粒进行了比较。当Ag（+）离子的浓度引起细胞活力的等效降低时，其代谢谱的变化与AgNPs的变化非常相似，主要区别在于对克雷布斯循环和能量代谢的影响较小。最后，本研究最新报道，虽然AgNPs和H2O2普遍下调糖酵解和破坏能量产生，但对一些代谢途径（GSH合成、谷氨酰胺水解和克雷布斯循环）的影响与ros介导的机制无关。总之，本研究表明核磁共振代谢组学能够定义AgNPs诱导的细微生化变化，并证明了该方法在快速、非靶向筛选纳米材料临床前毒性方面的潜力。
The widespread use of silver nanoparticles (AgNPs) is accompanied by a growing concern regarding their potential risks to human health, thus calling for an increased understanding of their biological effects. The aim of this work was to systematically study the extent to which changes in cellular metabolism were dependent on the properties of AgNPs, using NMR metabolomics. Human skin keratinocytes (HaCaT cells) were exposed to citrate-coated AgNPs of 10, 30 or 60nm diameter and to 30nm AgNPs coated either with citrate (CIT), polyethylene glycol (PEG) or bovine serum albumin (BSA), to assess the influence of NP size and surface chemistry. Overall, CIT-coated 60nm and PEG-coated 30nm AgNPs had the least impact on cell viability and metabolism. The role of ionic silver and reactive oxygen species (ROS)-mediated effects was also studied, in comparison to CIT-coated 30nm particles. At concentrations causing an equivalent decrease in cell viability, Ag(+)ions produced a change in the metabolic profile that was remarkably similar to that seen for AgNPs, the main difference being the lesser impact on the Krebs cycle and energy metabolism. Finally, this study newly reported that while down-regulated glycolysis and disruption of energy production were common to AgNPs and H2O2, the impact on some metabolic pathways (GSH synthesis, glutaminolysis and the Krebs cycle) was independent of ROS-mediated mechanisms. In conclusion, this study shows the ability of NMR metabolomics to define subtle biochemical changes induced by AgNPs and demonstrates the potential of this approach for rapid, untargeted screening of pre-clinical toxicity of nanomaterials in general.