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Investigating the toxic effects induced by iron oxide nanoparticles on neuroblastoma cell line: an integrative study combining cytotoxic, genotoxic and proteomic tools

机译:调查氧化铁纳米粒子诱导的神经母细胞瘤细胞系中诱导的毒性作用:细胞毒性,遗传毒性和蛋白质组学工具结合的一体化研究

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Nanomaterials have gained much attention for their use and benefit in several fields. Iron Oxide Nanoparticles (IONPs) have been used in Biomedicine as contrast agents for imaging cancer cells. However, several studies reported the potential toxicity of those nanoparticles in different models, especially in cells. Therefore, in our present study, we investigated the effects of IONPs on the SH-SY5Y neuroblastoma cell line. We carried out cytotoxic and genotoxic studies to evaluate the phenotypic effects, and proteomic investigation to evaluate the molecular effects and the mechanisms by which this kind of NPs could induce toxicity. Our results showed that the use of three different sizes of IONPs (14, 22 and 30 nm) induced cell detachment, cell morphological changes, size, and concentration-dependent IONP internalization and cell mortality. IONPs induced slight genotoxic damage assayed by modified comet assay without affecting cell cycle, mitochondrial function, membrane integrity, intracellular calcium level, and without inducing ROS generation. All the studies were performed to compare also the effects of IONPs to the ferric iron by incubating cells with equivalent concentration of FeCl3. In all tests, the NPs exhibited more toxicity than the ferric iron. The proteomic analysis followed by gene ontology and pathway analysis evidenced the effects of IONPs on cytoskeleton, cell apoptosis, and cancer development. Our findings provided more information about IONP effects on human cells and especially on cancer cell line.
机译:纳米材料在若干领域中使用和利益有很大的关注。氧化铁纳米颗粒(IONP)已用于生物医学中作为成像癌细胞的造影剂。然而,几项研究报告了这些纳米颗粒在不同模型中的潜在毒性,特别是在细胞中。因此,在我们目前的研究中,我们研究了IONP对SH-SY5Y神经母细胞瘤细胞系的影响。我们进行了细胞毒性和遗传毒性研究,以评估表型效应,蛋白质组学调查评估这种NPS可以诱导毒性的分子效应和机制。我们的研究结果表明,使用三种不同尺寸的IONP(14,22和30nm)诱导细胞分离,细胞形态变化,尺寸和浓度依赖性IONP内化和细胞死亡率。 IONP通过改性彗星测定诱导轻微的遗传毒性损伤,而不影响细胞周期,线粒体功能,膜完整性,细胞内钙水平,并且不诱导ROS产生。进行所有研究,以通过培养具有等效浓度的FECL3来比较IONP对铁铁的影响。在所有测试中,NPS表现出比铁铁更多的毒性。蛋白质组学分析随后基因本体论和途径分析证明了IONP对细胞骨架,细胞凋亡和癌症发育的影响。我们的调查结果提供了有关人体细胞的IONP效应的更多信息,特别是癌细胞系。

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