Mullaney M, Groth T, Darkow R, Hesse R, Albrecht W, Paul D, von Sengbusch G
GKSS Research Centre, Teltow, Germany.
Artif Organs. 1999 Jan;23(1):87-97. doi: 10.1046/j.1525-1594.1999.06280.x.
Particles with specific ligands for the adsorption of plasma proteins can be used in therapeutic or preparative apheresis. The development of these particles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functionalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and with tryptophan and histidine spaced with diamines of different length. Suitable protocols were developed for the washing of particles and the subsequent desorption of proteins adsorbed from human plasma. The adsorption pattern, as well as the quantification of the overall adsorption of proteins on these modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound human serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple correlations although in general more hydrophobic ligands bound higher quantities of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorption of fibrinogen expressed a different pattern. In this case, particular nanoparticles functionalized with aliphatic diamines bound significantly higher amounts of fibrinogen than all other ligands.
带有用于吸附血浆蛋白的特定配体的颗粒可用于治疗性或制备性血液成分单采。这些颗粒的开发可能受益于对蛋白质吸附与配体结构之间关系的更深入了解。用链长不断增加的脂肪族二胺、氨基酸赖氨酸、色氨酸、组氨酸及其相应的胺，以及用不同长度二胺间隔的色氨酸和组氨酸对纳米颗粒进行功能化。开发了合适的方案用于颗粒的洗涤以及随后从人血浆中吸附的蛋白质的解吸。用凝胶电泳研究了吸附模式以及蛋白质在这些修饰颗粒上的总吸附量的定量。随后进行免疫印迹，对结合的人血清白蛋白和纤维蛋白原进行特异性评估。蛋白质吸附与表面电荷密度和测量的疏水性的比较没有产生简单的相关性，尽管一般来说疏水性更强的配体结合的蛋白质量更高。人血清白蛋白的检测产生了类似的结果，因为在总蛋白质吸附中观察到了这种情况，而纤维蛋白原的吸附表现出不同的模式。在这种情况下，用脂肪族二胺功能化的特定纳米颗粒结合的纤维蛋白原量明显高于所有其他配体。
