Department of Environmental Medicine, University of Rochester, Rochester, New York 14624, USA.
J Toxicol Environ Health A. 2010;73(5):445-61. doi: 10.1080/15287390903489422.
Engineered nanoparticles (NP) are being developed and incorporated in a number of commercial products, raising the potential of human exposure during manufacture, use, and disposal. Although data concerning the potential toxicity of some NP have been reported, validated simple assays are lacking for predicting their in vivo toxicity. The aim of this study was to evaluate new response metrics based on chemical and biological activity of NP for screening assays that can be used to predict NP toxicity in vivo. Two cell-free and two cell-based assays were evaluated for their power in predicting in vivo toxicity of eight distinct particle types with widely differing physicochemical characteristics. The cell-free systems comprised fluorescence- and electron spin resonance-based assays of oxidant activity. The cell-based systems also used electron spin resonance (ESR) as well as luciferase reporter activity to rank the different particle types in comparison to benchmark particles of low and high activity. In vivo experiments evaluated acute pulmonary inflammatory responses in rats. Endpoints in all assays were related to oxidative stress and responses were expressed per unit NP surface area to compare the results of different assays. Results indicated that NP are capable of producing reactive species, which in biological systems lead to oxidative stress. Copper NP had the greatest activity in all assays, while TiO(2) and gold NP generally were the least reactive. Differences in the ranking of NP activity among the assays were found when comparisons were based on measured responses. However, expressing the chemical (cell-free) and biological (cells; in vivo) activity per unit particle surface area showed that all in vitro assays correlated significantly with in vivo results, with the cellular assays correlating the best. Data from this study indicate that it is possible to predict acute in vivo inflammatory potential of NP with cell-free and cellular assays by using NP surface area-based dose and response metrics, but that a cellular component is required to achieve a higher degree of predictive power.
纳米颗粒（NP）正在被开发并应用于许多商业产品中，这增加了在制造、使用和处置过程中人类暴露的可能性。虽然已经有一些关于某些 NP 潜在毒性的数据被报道，但是缺乏用于预测其体内毒性的经过验证的简单检测方法。本研究的目的是评估基于 NP 的化学和生物学活性的新的反应指标，以筛选可用于预测 NP 体内毒性的检测方法。评估了两种无细胞和两种基于细胞的检测方法，以评估它们预测具有广泛不同理化特性的 8 种不同类型的 NP 体内毒性的能力。无细胞系统包括基于荧光和电子自旋共振的氧化剂活性检测方法。基于细胞的系统还使用电子自旋共振（ESR）和荧光素酶报告活性，将不同的颗粒类型与低活性和高活性的基准颗粒进行比较。体内实验评估了大鼠急性肺部炎症反应。所有检测方法的终点均与氧化应激有关，并按 NP 单位表面积表达反应，以比较不同检测方法的结果。结果表明，NP 能够产生活性物质，这些物质在生物系统中导致氧化应激。所有检测方法中，铜 NP 的活性最大，而 TiO(2)和金 NP 通常反应性最低。基于测量的反应，在检测方法之间对 NP 活性进行排序时，发现了差异。然而，按单位颗粒表面积表示化学（无细胞）和生物学（细胞；体内）活性表明，所有体外检测方法与体内结果显著相关，细胞检测方法相关性最好。这项研究的数据表明，通过使用基于 NP 表面积的剂量和反应指标，使用无细胞和细胞检测方法，有可能预测 NP 的急性体内炎症潜力，但需要细胞成分才能实现更高的预测能力。
