Moe Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Biomaterials. 2010 Nov;31(32):8465-74. doi: 10.1016/j.biomaterials.2010.07.060. Epub 2010 Aug 10.
In spite of significant advantages exhibiting in the applications of silicon dioxide particles in biological and medicine fields, their adverse effects still remain a big concern. Herein monodisperse spherical SiO(2) particles with diameters of 80 nm and 500 nm were used to study their interactions with human dermal fibroblasts. Both the particles were readily internalized into the fibroblasts within a short time. The 500 nm particles were taken up in a larger amount through macropinocytosis and clathrin-mediated endocytosis pathways, whereas uptake of the 80 nm SiO(2) particles was mediated corporately by macropinocytosis, clathrin-mediated and caveolae-mediated endocytosis. The particles mainly dispersed in the cytoplasm or resided within the lysosomal vesicles, but could not enter into the cell nucleus within 24 h culture in vitro. Treatment with the 80 nm SiO(2) particles caused apparently decrease of cell viability and also weakened the mitochondrial membrane potential. Further experiments demonstrated that the cell adhesion and migration were greatly affected by uptake of the SiO(2) particles regardless of their size. RT-PCR results indicated down regulation of the mRNA expression of adhesion relevant genes, i.e. fibronectin, laminin and focal adhesion kinase (FAK).
尽管二氧化硅颗粒在生物和医学领域的应用具有显著优势，但它们的不良反应仍然令人担忧。在此，我们使用直径为 80nm 和 500nm 的单分散球形二氧化硅颗粒来研究它们与人类真皮成纤维细胞的相互作用。两种颗粒都在短时间内很容易被成纤维细胞内化。500nm 颗粒通过巨胞饮作用和网格蛋白介导的内吞作用途径被大量摄取，而 80nmSiO2 颗粒的摄取则通过巨胞饮作用、网格蛋白介导和 caveolae 介导的内吞作用共同介导。这些颗粒主要分散在细胞质或溶酶体小泡中，但在体外培养 24 小时内不能进入细胞核。用 80nmSiO2 颗粒处理后，细胞活力明显下降，线粒体膜电位也减弱。进一步的实验表明，无论颗粒大小如何，细胞的黏附和迁移都受到颗粒摄取的显著影响。RT-PCR 结果表明，细胞黏附相关基因（如纤连蛋白、层粘连蛋白和粘着斑激酶）的 mRNA 表达下调。
