Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z7, Canada.
Int J Mol Sci. 2024 Oct 4;25(19):10710. doi: 10.3390/ijms251910710.
Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.
肾功能障碍导致血液中代谢物的滞留,这些代谢物无法通过常规血液透析有效清除。基于磁性纳米颗粒 (MNP) 的吸附剂具有固有特性,使其易于捕获血液中的毒素,特别是具有较大的表面积,可通过化学修饰来增强毒素捕获能力,并且可以使用外部磁场从血液中轻松收集。环糊精 (CD) 呈现出一种化学结构,有利于小分子的结合。然而,用不同天然类型的 CD(α、β 或 γ)制成的薄膜修饰的 MNPs 的血液相容性尚未得到研究,这对于将 MNPs 潜在应用于补充血液透析至关重要。为此,在 MNPs 上形成了 α、β 或 γ-CD 的薄膜,并对其进行了表征。评估了这些薄膜对吸附蛋白结构、关键吸附蛋白组成和凝血动力学的影响。结果发现,修饰后的 MNPs 不会显著影响某些蛋白质(白蛋白、溶菌酶、α-乳白蛋白)的二级结构。评估了血小板贫乏的人血浆中的吸附蛋白质组作为薄膜性质的函数。与未修饰的纳米颗粒相比,CD 修饰的 MNPs 吸附到 MNPs 表面积上的蛋白质显著减少。免疫印迹结果表明,CD 修饰的 MNPs 吸附的 C3、纤维蛋白原、抗凝血酶、因子 XI 和纤溶酶原水平存在差异。血液相容性实验表明,CD 修饰的 MNPs 与人全血相容,对血小板活化、溶血或止血没有明显影响。