Polymer Standards Section Japan, National Metrology Institute of Japan, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, Higashi 1-1-1, Tsukuba, Ibaraki 305-8565, Japan.
Toxicol In Vitro. 2010 Apr;24(3):1009-18. doi: 10.1016/j.tiv.2009.12.006. Epub 2009 Dec 13.
The aim of this study is to characterize the dispersion characteristics of various metal oxide nanoparticles and secondary nanoparticle formation in culture medium. Many studies have already investigated the in vitro toxicities of various metal oxide nanoparticles; however, there have been few discussions about the particle transport mode to cells during a period of toxicity assessment. The particle transport mode would strongly affect the amount of uptake by cells; therefore, estimation of the transport mode for various metal oxide particles is important. Fourteen different metal oxide nanoparticle dispersions in a culture medium were examined. The sizes of the secondary nanoparticles were observed to be larger than 100 nm by dynamic light scattering (DLS). According to Stokes law and the Stokes-Einstein assumption, pure metal oxide particles with such sizes should gravitationally settle faster than diffusion processes; however, the secondary metal oxide particles examined in this study exhibited unexpectedly slower gravitational settling rates. The slow gravitational settling kinetics of particles was estimated to be caused by the inclusion of protein into the secondary nanoparticles, which resulted in lower densities than the pure metal oxide particles. The ratios of metal oxide to protein in secondary particles could be affected by the protein adsorption ability of the corresponding metal oxide primary particles. To the best of our knowledge, it was clarified for the first time that stably dispersed secondary metal oxide nanoparticles with slow gravitational settling kinetics are induced by secondary nanoparticles consisting of small amounts of metal oxide particles and large amounts of protein, which results in lower particle densities than the pure metal oxide particles. The estimation of particle dynamics in culture medium using this method would be significant to recognize the inherent toxicity of nanoparticles.
本研究的目的是描述各种金属氧化物纳米粒子在培养基中的分散特性和次级纳米粒子的形成。许多研究已经调查了各种金属氧化物纳米粒子的体外毒性；然而，对于在毒性评估期间颗粒向细胞的传输模式，仅有少数讨论。颗粒的传输模式将强烈影响细胞的摄取量；因此，对各种金属氧化物颗粒的传输模式进行估计是很重要的。本研究考察了培养基中 14 种不同的金属氧化物纳米粒子分散体。通过动态光散射（DLS）观察到次级纳米粒子的尺寸大于 100nm。根据 Stokes 定律和 Stokes-Einstein 假设，具有这种尺寸的纯金属氧化物颗粒应该比扩散过程更快地沉降；然而，本研究中检查的次级金属氧化物颗粒表现出出人意料的较慢的重力沉降速率。颗粒缓慢的重力沉降动力学被估计是由于蛋白质包含在次级纳米粒子中，导致密度低于纯金属氧化物颗粒。次级粒子中金属氧化物与蛋白质的比例可能受到相应金属氧化物初级粒子的蛋白质吸附能力的影响。据我们所知，首次阐明了由少量金属氧化物颗粒和大量蛋白质组成的次级纳米粒子诱导具有缓慢重力沉降动力学的稳定分散的次级金属氧化物纳米粒子，导致颗粒密度低于纯金属氧化物颗粒。使用这种方法估计培养基中的颗粒动力学对于认识纳米颗粒的固有毒性具有重要意义。
