a Group of Nanoparticles and Nanocomposites, Crystallography Department , Institut de Ciència de Materials de Barcelona, ICMAB-CSIC , Barcelona , Campus UAB , Spain.
b Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering , Jinan University , Guangzhou , China.
Nanotoxicology. 2017 Jun;11(5):647-657. doi: 10.1080/17435390.2017.1342011. Epub 2017 Jul 4.
We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated. The role of oxidative stress was confirmed by gene expression analysis and by synchrotron Fourier Transform infrared microscopy based on the higher tissue oxidation of NP-treated animals. The observed transcriptional modulation of key signaling pathways such as MAPK and Wnt suggests that SPIONs might be endocytosed by clathrin-mediated processes, a putative mechanism of nanotoxicity which deserves further mechanistic investigations.
我们结合全基因组分析和经常与纳米毒性相关的特定分子标记物的研究，对氧化铁纳米颗粒（SPION）在秀丽隐杆线虫中的作用进行了机制研究。探索了两种不同涂层的效果：柠檬酸，一种阴离子稳定剂，和牛血清白蛋白，作为预先形成的蛋白质外壳。转录组学研究鉴定了暴露于 SPION 后差异表达的基因。定量评估了参与氧化应激、金属解毒反应、内吞作用、肠道完整性和铁稳态的基因的表达。通过基因表达分析和基于同步加速器傅里叶变换红外显微镜的组织氧化更高，证实了氧化应激的作用，NP 处理动物。观察到的关键信号通路（如 MAPK 和 Wnt）的转录调节表明，SPION 可能通过网格蛋白介导的过程被内吞，这是一种潜在的纳米毒性机制，值得进一步进行机制研究。
