Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
Eur J Pharm Biopharm. 2011 Apr;77(3):376-83. doi: 10.1016/j.ejpb.2010.10.013. Epub 2010 Nov 5.
The alveolar lining fluid (ALF) covering the respiratory epithelium of the deep lung is the first biological barrier encountered by nanoparticles after inhalation. We here report for the first time significant differences for metal oxide nanoparticles to the binding of surfactant protein A (SP-A), the predominant protein component of ALF. SP-A is a physiologically most relevant protein and provides important biological signals. Also, it is involved in the lung's immune defence, controlling e.g. particle binding, uptake or transcytosis by epithelial cells and macrophages. In our study, we could prove different particle-protein interaction for eight different nanoparticles, whereas particles of the same bulk material revealed different adsorption patterns. In contrast to other proteins as bovine serum albumin (BSA), SP-A does not seem to significantly deagglomerate large agglomerates of particles, indicating different adsorption mechanisms as in the well-investigated model protein BSA. These findings may have important consequences for biological fate and toxicological effects of inhaled nanomaterials.
肺泡衬液(ALF)覆盖着深层肺部的呼吸上皮,是吸入后纳米颗粒首先遇到的第一道生物屏障。我们首次报道了金属氧化物纳米颗粒与表面活性蛋白 A(SP-A)的显著差异,SP-A 是 ALF 中主要的蛋白质成分。SP-A 是一种与生理相关性最强的蛋白质,提供了重要的生物学信号。此外,它还参与了肺部的免疫防御,控制例如颗粒与上皮细胞和巨噬细胞的结合、摄取或转胞吞作用。在我们的研究中,我们能够证明对于八种不同的纳米颗粒存在不同的颗粒-蛋白相互作用,而相同块状材料的颗粒则显示出不同的吸附模式。与牛血清白蛋白(BSA)等其他蛋白质不同,SP-A 似乎不会显著解聚大的颗粒团聚体,这表明与经过充分研究的模型蛋白 BSA 的吸附机制不同。这些发现可能对吸入纳米材料的生物命运和毒理学效应产生重要影响。