The effect of shear flow on nanoparticle agglomeration and deposition in <i>in vitro</i> dynamic flow models
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Traditional <i>in vitro</i> toxicity experiments typically involve exposure of a mono- or co-culture of cells to nanoparticles (NPs) in static conditions with the assumption of 100% deposition (i.e. dose) of well-dispersed particles. However, cellular dose can be affected by agglomeration and the unique transport kinetics of NPs in biological media. We hypothesize that shear flow can address these issues and achieve more predictable dosage. Here, we compare the behavior of gold NPs with diameters of 5, 10 and 30 nm in static and dynamic <i>in vitro</i> models. We also utilize transport modeling to approximate the shear rate experienced by the cells in dynamic conditions to evaluate physiological relevance. The transport kinetics show that NP behavior is governed by both gravity and diffusion forces in static conditions and only diffusion in dynamic conditions. Our results reveal that dynamic systems are capable of producing a more predictable dose compared to static systems, which has strong implications for improving repeatability in nanotoxicity assessments.
传统的体外(in vitro)毒性实验通常将单细胞或共培养细胞置于静态条件下,使其暴露于纳米颗粒(nanoparticles,缩写NPs)中,并默认分散良好的颗粒可100%沉积(即给药剂量)。然而,细胞实际摄取的剂量会受到纳米颗粒在生物介质中的团聚现象以及独特的输运动力学的影响。本研究提出假说:剪切流可解决上述问题,实现更可预测的给药剂量。在本研究中,我们对比了直径分别为5、10和30 nm的金纳米颗粒在静态与动态体外模型中的行为表现。同时,我们借助输运模型,对动态条件下细胞所受的剪切速率进行估算,以评估其生理相关性。输运动力学分析结果表明:静态条件下纳米颗粒的行为受重力与扩散力共同调控,而动态条件下仅受扩散力主导。本研究结果显示,相较于静态体系,动态体系可实现更具可预测性的剂量,这对提升纳米毒性评估的重复性具有重要意义。




