Department of Molecular Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon 443-749, Korea,
Arch Toxicol. 2013 Jul;87(7):1219-30. doi: 10.1007/s00204-013-1019-3. Epub 2013 Feb 7.
In this study, we compared their toxicity in vivo and in vitro based on the physicochemical properties of three different types of TiO₂ nanowires, H₂Ti₃O₇ nanowires (1HTO), hydrothermal treatment (2HTO), and calcination (3HTO) of 1HTO. The surface of 1HTO was smooth, and the surface of 2HTO was much rougher. The negative charge on the surface increased in the order of 2HTO, 3HTO, and 1HTO, whereas the surface area increased in the order of 3HTO, 1HTO, and 2HTO. The lung is a main exposure route of nanoparticles. On day 28 after a single instillation (1 mg/kg), three nanowires induced a Th2-type inflammatory response together with the relative increase in CD4⁺ T cells, especially by 2HTO. In vitro, three TiO₂ nanowires (10 μg/ml) commonly induced the generation of cell debris in eight cell lines which may be the potential target organ of nanoparticles, especially by 2HTO. It seemed that the generation of cell debris coincides with the increase in autophagosome-like vacuoles in the cytosol. In further study using BEAS-2B cells originated from the lung, the protein amount from cells exposed to 2HTO decreased more clearly although the generation of reactive oxygen species (ROS) was less compared to 1HTO and 3HTO. Based on these results, we suggest that surface area may act as an important factor depends on the biological response by TiO₂ nanowires. Furthermore, the increase in autophagosome-like vacuoles may be an important cause of cell death by nanoparticles with ROS.
在这项研究中，我们根据三种不同类型的 TiO₂ 纳米线的物理化学性质，比较了它们在体内和体外的毒性。这三种不同类型的 TiO₂ 纳米线分别是：H₂Ti₃O₇ 纳米线（1HTO）、水热处理（2HTO）和 1HTO 的煅烧（3HTO）。1HTO 的表面光滑，而 2HTO 的表面则更加粗糙。表面负电荷的增加顺序为 2HTO、3HTO 和 1HTO，而比表面积的增加顺序为 3HTO、1HTO 和 2HTO。肺部是纳米颗粒的主要暴露途径。在单次滴注（1mg/kg）后的第 28 天，三种纳米线共同引起了 Th2 型炎症反应，同时伴随着 CD4⁺T 细胞的相对增加，尤其是 2HTO。在体外，三种 TiO₂ 纳米线（10μg/ml）通常会在八种细胞系中诱导细胞碎片的产生，这可能是纳米颗粒的潜在靶器官，尤其是 2HTO。似乎细胞碎片的产生与细胞质中自噬体样空泡的增加相吻合。在使用源自肺部的 BEAS-2B 细胞进行的进一步研究中，与 1HTO 和 3HTO 相比，暴露于 2HTO 的细胞中蛋白质含量的减少更为明显，尽管活性氧（ROS）的产生较少。基于这些结果，我们认为比表面积可能是 TiO₂ 纳米线产生生物学反应的一个重要因素。此外，自噬体样空泡的增加可能是纳米颗粒引起细胞死亡的一个重要原因，而 ROS 则是其中之一。
