Cellular Functional Nanobiomaterials Group, Research Center for Functional Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Biomater Sci. 2017 May 2;5(5):1014-1021. doi: 10.1039/c6bm00946h.
The size of titanium dioxide (TiO) nanoparticles is a vital parameter that determines their cytotoxicity. However, most reported studies have employed irregular shapes and sizes of TiO nanoparticles, as it is difficult to produce nanoparticles of suitable sizes for research. We produced good model TiO nanoparticles of uniform shape and size for use in studying their cytotoxicity. In this work, spherical, uniform polyethylene glycol-modified TiO (TiO-PEG) nanoparticles of differing sizes (100, 200, and 300 nm) were prepared using the sol-gel method. A size-dependent decrease in cell viability was observed with increasing nanoparticle size. Furthermore, apoptosis was found to be positively associated with nanoparticle size, as evidenced by an increase in caspase-3 activity with increasing nanoparticle size. Larger nanoparticles exhibited higher cellular uptake, suggesting that larger nanoparticles more strongly induce apoptosis. In addition, the cellular uptake of different sizes of nanoparticles was energy dependent, suggesting that there are size-dependent uptake pathways. We found that 100 and 200 nm (but not 300 nm) nanoparticles were taken up via clathrin-mediated endocytosis. These results utilizing uniform nanoparticles suggest that the size-dependent cytotoxicity of nanoparticles involves active cellular uptake, caspase-3 activation, and apoptosis in the epithelial cell line (NCI-H292). These findings will hopefully aid in the future design and safe use of nanoparticles.
二氧化钛 (TiO) 纳米颗粒的尺寸是决定其细胞毒性的一个重要参数。然而，大多数报道的研究都采用了不规则形状和尺寸的 TiO 纳米颗粒，因为很难生产出适合研究的纳米颗粒。我们制备了具有良好形貌和尺寸均匀性的 TiO 纳米颗粒模型，用于研究其细胞毒性。在这项工作中，我们使用溶胶-凝胶法制备了具有不同尺寸（100、200 和 300nm）的球形、均匀的聚乙二醇修饰的 TiO（TiO-PEG）纳米颗粒。随着纳米颗粒尺寸的增加，细胞活力呈明显下降趋势。此外，细胞凋亡与纳米颗粒尺寸呈正相关，随着纳米颗粒尺寸的增加，caspase-3 活性增加。较大的纳米颗粒表现出更高的细胞摄取，表明较大的纳米颗粒更能诱导细胞凋亡。此外，不同尺寸的纳米颗粒的细胞摄取依赖于能量，表明存在尺寸依赖性摄取途径。我们发现 100nm 和 200nm（但不是 300nm）纳米颗粒通过网格蛋白介导的内吞作用被摄取。这些利用均匀纳米颗粒的结果表明，纳米颗粒的尺寸依赖性细胞毒性涉及上皮细胞系（NCI-H292）中的主动细胞摄取、caspase-3 激活和细胞凋亡。这些发现有望为纳米颗粒的未来设计和安全使用提供帮助。
