Cathe Deidre S, Whitaker Jasmine N, Breitner Emily K, Comfort Kristen K
Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA.
Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA.
Toxicol Lett. 2017 Feb 15;268:1-7. doi: 10.1016/j.toxlet.2017.01.003. Epub 2017 Jan 16.
Nanoparticles (NPs) possess distinctive physicochemical properties that in addition to differentiating them from their bulk counterparts can induce negative cellular consequences. Standard in vitro systems have served as the primary model for NP safety evaluations, but suffer from a lack physiological relevance. One way to overcome this limitation and evaluate NP characteristics under more accurate conditions is through the use of artificial physiological fluids, which mimic the composition of in vivo environments. In this study, we identified that copper oxide (CuO) and titanium dioxide (TiO) NPs displayed modified behavior when dispersed in artificial interstitial fluid (IF) versus traditional media, including extensive agglomeration and increased particle deposition. When keratinocyte cells underwent CuO NP exposure, synergistic stress and toxicity responses occurred within an IF environment, correlating with augmented particle deposition. However, following IF incubation alone or concurrently with TiO NPs, which are not innately toxic, no combinatorial responses were identified. These results indicate that synergistic outcomes arise when toxic NPs undergo fluid-induced alterations to key physicochemical properties and behaviors. This study highlights the necessity of carrying out NP characterization and safety assessments in physiologically-representative environments; as altered behavior patterns have the potential to induce bioresponses not identified within traditional models.
纳米颗粒（NPs）具有独特的物理化学性质，这些性质不仅使其有别于其块状对应物，还可能引发负面的细胞效应。标准的体外系统一直是纳米颗粒安全性评估的主要模型，但缺乏生理相关性。克服这一局限性并在更准确的条件下评估纳米颗粒特性的一种方法是使用人工生理流体，其模拟体内环境的组成。在本研究中，我们发现氧化铜（CuO）和二氧化钛（TiO）纳米颗粒分散在人工组织液（IF）中与传统介质相比表现出不同的行为，包括广泛的团聚和颗粒沉积增加。当角质形成细胞暴露于氧化铜纳米颗粒时，在组织液环境中会发生协同应激和毒性反应，这与颗粒沉积增加相关。然而，单独或与本质无毒的二氧化钛纳米颗粒同时进行组织液孵育后，未发现联合反应。这些结果表明，当有毒纳米颗粒因流体诱导而导致关键物理化学性质和行为发生改变时，会产生协同效应。本研究强调了在具有生理代表性的环境中进行纳米颗粒表征和安全性评估的必要性；因为行为模式的改变有可能引发传统模型中未发现的生物反应。
