论文标题

在细胞培养物中银纳米粒子剂量测定的硅方法中的整合体外

An integrated in vitro in silico approach for silver nanoparticle dosimetry in cell cultures

论文作者

Poli1, Daniele, Mattei, Giorgio, Ucciferri, Nadia, Ahluwalia, Arti

论文摘要

在过去的十年中,生命有机体暴露于银纳米颗粒(AG NPS)引起的潜在人类和环境危害一直是深入讨论的主题。尽管在生物医学应用中使用了Ag NP的使用日益增长,但仍需要对毒性作用的定量,这是银质量到达细胞的函数(即靶细胞剂量)。为了提供更准确的剂量反应分析,我们提出了一种结合良好的计算方法和实验方法的新型综合方法。我们首先使用了Thomas及其同事(2018)提出的特定动力学模型(ISD3),以在静态库维特实验中对计算的AG NP沉积进行实验验证。验证后,使用ISD3来预测在96个井板中培养的人类内皮细胞和肝细胞的总质量。然后在培养后24小时测得的细胞活力与该靶细胞剂量有关。我们的结果表明,暴露24小时后细胞单层感知的剂量比管理的名义培养基浓度低约85%。因此,应使用粒子特征和实验条件(例如,井的时间,大小和形状)的精确剂量测定法,以更好地解释由银进入细胞的量引起的效果。

Potential human and environmental hazards resulting from the exposure of living organisms to silver nanoparticles (Ag NPs) have been the subject of intensive discussion in the last decade. Despite the growing use of Ag NPs in biomedical applications, a quantification of the toxic effects as a function of the total silver mass reaching cells (namely, target cell dose) is still needed. To provide a more accurate dose-response analysis, we propose a novel integrated approach combining well-established computational and experimental methodologies. We first used the particokinetic model (ISD3) proposed by Thomas and colleagues (2018) for providing experimental validation of computed Ag NP sedimentation in static-cuvette experiments. After validation, ISD3 was employed to predict the total mass of silver reaching human endothelial cells and hepatocytes cultured in 96 well plates. Cell viability measured after 24h of culture was then related to this target cell dose. Our results show that the dose perceived by the cell monolayer after 24 h of exposure is around 85% lower than the administered nominal media concentration. Therefore, accurate dosimetry considering particle characteristics and experimental conditions (e.g., time, size and shape of wells) should be employed for better interpreting effects induced by the amount of silver reaching cells.

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