Burns Katherine E, Uhrig Robert F, Jewett Maggie E, Bourbon Madison F, Krupa Kristen A
Department of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469-0256, USA.
Antioxidants (Basel). 2021 May 23;10(6):832. doi: 10.3390/antiox10060832.
Silver nanoparticles (AgNPs) are being employed in numerous consumer goods and applications; however, they are renowned for inducing negative cellular consequences including toxicity, oxidative stress, and an inflammatory response. Nanotoxicological outcomes are dependent on numerous factors, including physicochemical, biological, and environmental influences. Currently, NP safety evaluations are carried out in both cell-based in vitro and animal in vivo models, with poor correlation between these mechanisms. These discrepancies highlight the need for enhanced exposure environments, which retain the advantages of in vitro models but incorporate critical in vivo influences, such as fluid dynamics. This study characterized the effects of dynamic flow on AgNP behavior, cellular interactions, and oxidative stress within both adherent alveolar (A549) and suspension monocyte (U937) models. This study determined that the presence of physiologically relevant flow resulted in substantial modifications to AgNP cellular interactions and subsequent oxidative stress, as assessed via reactive oxygen species (ROS), glutathione levels, p53, NFκB, and secretion of pro-inflammatory cytokines. Within the adherent model, dynamic flow reduced AgNP deposition and oxidative stress markers by roughly 20%. However, due to increased frequency of contact, the suspension U937 cells were associated with higher NP interactions and intracellular stress under fluid flow exposure conditions. For example, the increased AgNP association resulted in a 50% increase in intracellular ROS and p53 levels. This work highlights the potential of modified in vitro systems to improve analysis of AgNP dosimetry and safety evaluations, including oxidative stress assessments.
银纳米颗粒（AgNPs）正被应用于众多消费品和应用领域；然而，它们因会引发包括毒性、氧化应激和炎症反应在内的负面细胞效应而闻名。纳米毒理学结果取决于多种因素，包括物理化学、生物学和环境影响。目前，纳米颗粒安全性评估是在基于细胞的体外模型和动物体内模型中进行的，这些机制之间的相关性较差。这些差异凸显了对增强暴露环境的需求，这种环境保留了体外模型的优势，但纳入了关键的体内影响因素，如流体动力学。本研究表征了动态流动对贴壁肺泡（A549）和悬浮单核细胞（U937）模型中AgNP行为、细胞相互作用和氧化应激的影响。本研究确定，通过活性氧（ROS）、谷胱甘肽水平、p53、NFκB以及促炎细胞因子的分泌评估发现，生理相关流动的存在导致AgNP细胞相互作用以及随后的氧化应激发生了显著改变。在贴壁模型中，动态流动使AgNP沉积和氧化应激标志物减少了约20%。然而，由于接触频率增加，在流体流动暴露条件下，悬浮的U937细胞与更高的纳米颗粒相互作用和细胞内应激相关。例如，AgNP结合增加导致细胞内ROS和p53水平增加了50%。这项工作凸显了改良体外系统在改进AgNP剂量测定分析和安全性评估（包括氧化应激评估）方面的潜力。
