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The cytotoxicity of polycationic iron oxide nanoparticles: Common endpoint assays and alternative approaches for improved understanding of cellular response mechanism

机译:聚阳离子氧化铁纳米颗粒的细胞毒性:通用终点分析和替代方法可增进对细胞应答机制的了解

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摘要

BackgroundIron oxide magnetic nanoparticles (MNP's) have an increasing number of biomedical applications. As such in vitro characterisation is essential to ensure the bio-safety of these particles. Little is known on the cellular interaction or effect on membrane integrity upon exposure to these MNPs. Here we synthesised Fe3O4 and surface coated with poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG) to achieve particles of varying surface positive charges and used them as model MNP's to evaluate the relative utility and limitations of cellular assays commonly applied for nanotoxicity assessment. An alternative approach, atomic force microscopy (AFM), was explored for the analysis of membrane structure and cell morphology upon interacting with the MNPs. The particles were tested in vitro on human SH-SY5Y, MCF-7 and U937 cell lines for reactive oxygen species (ROS) production and lipid peroxidation (LPO), LDH leakage and their overall cytotoxic effect. These results were compared with AFM topography imaging carried out on fixed cell lines.
机译:背景技术氧化铁磁性纳米颗粒(MNP's)具有越来越多的生物医学应用。因此,体外表征对于确保这些颗粒的生物安全性至关重要。接触这些MNP时,细胞相互作用或对膜完整性的影响知之甚少。在这里,我们合成了Fe3O4,并在表面涂覆了聚(乙烯亚胺)(PEI)和聚(乙二醇)(PEG),以实现具有不同表面正电荷的颗粒,并将它们用作模型MNP,以评估常用细胞分析法的相对效用和局限性用于纳米毒性评估。探索了一种替代方法,原子力显微镜(AFM),用于在与MNP相互作用后分析膜结构和细胞形态。在人SH-SY5Y,MCF-7和U937细胞系上体外测试了这些颗粒的活性氧(ROS)产生和脂质过氧化(LPO),LDH泄漏及其总体细胞毒性作用。将这些结果与在固定细胞系上进行的AFM形貌成像进行了比较。

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