Tyumentseva Anna, Khilazheva Elena, Petrova Valeria, Stolyar Sergey
Federal Research Center, Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences, Akademgorodok st. 50, Krasnoyarsk 660036, Russia.
Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky, Ministry of Health of the Russian Federation, 660022, Partizana Zheleznyaka St. 1, Krasnoyarsk, Russia.
Toxicol In Vitro. 2024 Jun;98:105829. doi: 10.1016/j.tiv.2024.105829. Epub 2024 Apr 12.
Iron oxide nanoparticles (IONPs) are considered as the most biocompatible magnetic materials suitable for biomedical applications. Nevertheless, there are many evidences of their toxicity for living organisms and partially neurotoxicity. The central nervous system is protected from undesirable substances circulating in the bloodstream by the blood-brain barrier (BBB). And even if being small enough, some nanoparticles could be able to penetrate cell membranes in other cells but will often be delayed by the BBB cells. However, the neurotoxicity of iron oxide is described even in the cases when IONPs should not uptake to the nervous system by experimental design. The aim of this study was to investigate what molecular changes in the cells-components of BBB - endotheliocytes and underlying astrocytes - may be caused by IONPs in the blood vessels of the brain. For this, a two-layer in vitro BBB model was created, consisting of rat cerebral endothelial cells and astrocytes. It was revealed that 100 and 200 mg/L of the nanoparticles induce metabolism alteration in the cells under study. Using RNA-sequencing, the up-regulation of pro-inflammatory chemokines encoding genes and changes in the expression of genes associated with detoxification in the endotheliocytes were demonstrated under the influence of 100 mg/L IONPs.
氧化铁纳米颗粒（IONPs）被认为是最具生物相容性的磁性材料，适用于生物医学应用。然而，有许多证据表明它们对生物体具有毒性，并且具有部分神经毒性。血脑屏障（BBB）可保护中枢神经系统免受血液循环中有害物质的侵害。即使纳米颗粒足够小，一些纳米颗粒能够穿透其他细胞的细胞膜，但通常会被血脑屏障细胞阻挡。然而，即使在实验设计中IONPs不应摄取到神经系统的情况下，也有关于氧化铁神经毒性的描述。本研究的目的是调查IONPs可能会导致血脑屏障的细胞成分（内皮细胞和下层星形胶质细胞）发生哪些分子变化。为此，创建了一个由大鼠脑内皮细胞和星形胶质细胞组成的双层体外血脑屏障模型。结果显示，100和200mg/L的纳米颗粒会诱导所研究细胞的代谢改变。使用RNA测序技术，在100mg/L IONPs的影响下，证明了内皮细胞中促炎趋化因子编码基因的上调以及与解毒相关基因表达的变化。
