Braakhuis Hedwig M, Kloet Samantha K, Kezic Sanja, Kuper Frieke, Park Margriet V D Z, Bellmann Susann, van der Zande Meike, Le Gac Séverine, Krystek Petra, Peters Ruud J B, Rietjens Ivonne M C M, Bouwmeester Hans
Department of Toxicogenomics, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
Arch Toxicol. 2015 Sep;89(9):1469-95. doi: 10.1007/s00204-015-1518-5. Epub 2015 May 15.
The increasing use of nanoparticles in products likely results in increased exposure of both workers and consumers. Because of their small size, there are concerns that nanoparticles unintentionally cross the barriers of the human body. Several in vivo rodent studies show that, dependent on the exposure route, time, and concentration, and their characteristics, nanoparticles can cross the lung, gut, skin, and placental barrier. This review aims to evaluate the performance of in vitro models that mimic the barriers of the human body, with a focus on the lung, gut, skin, and placental barrier. For these barriers, in vitro models of varying complexity are available, ranging from single-cell-type monolayer to multi-cell (3D) models. Only a few studies are available that allow comparison of the in vitro translocation to in vivo data. This situation could change since the availability of analytical detection techniques is no longer a limiting factor for this comparison. We conclude that to further develop in vitro models to be used in risk assessment, the current strategy to improve the models to more closely mimic the human situation by using co-cultures of different cell types and microfluidic approaches to better control the tissue microenvironments are essential. At the current state of the art, the in vitro models do not yet allow prediction of absolute transfer rates but they do support the definition of relative transfer rates and can thus help to reduce animal testing by setting priorities for subsequent in vivo testing.
纳米颗粒在产品中的使用日益增加，这可能导致工人和消费者接触纳米颗粒的机会增多。由于纳米颗粒尺寸小，人们担心它们会意外穿过人体屏障。多项啮齿动物体内研究表明，根据暴露途径、时间、浓度及其特性，纳米颗粒能够穿过肺、肠道、皮肤和胎盘屏障。本综述旨在评估模拟人体屏障的体外模型的性能，重点关注肺、肠道、皮肤和胎盘屏障。对于这些屏障，有不同复杂程度的体外模型可供选择，从单细胞类型的单层模型到多细胞（3D）模型。仅有少数研究能够将体外转运情况与体内数据进行比较。随着分析检测技术不再是这种比较的限制因素，这种情况可能会改变。我们得出结论，为了进一步开发用于风险评估的体外模型，当前通过使用不同细胞类型的共培养和微流控方法来更好地控制组织微环境，从而使模型更紧密地模拟人体情况的策略至关重要。在当前技术水平下，体外模型尚无法预测绝对转运速率，但它们确实有助于确定相对转运速率，因此可以通过为后续体内试验设定优先级来帮助减少动物试验。
