Department of Chemical and Material Engineering, University of Alberta, Edmonton, AB T6G 1H9, Canada.
Int J Mol Sci. 2024 Nov 7;25(22):11975. doi: 10.3390/ijms252211975.
Kidney failure leads to the accumulation of metabolites in the blood compartment. This build-up of metabolites has been associated with increased mortality and morbidity in these patients; thus, these metabolites are commonly called uremic toxins. The retention of some uremic toxins in the blood results from a strong interaction with serum albumin, preventing their clearance using standard hemodialysis techniques. Adsorbents are considered the next-generation technology for clearing uremic toxins from the blood, and iron oxide magnetic nanoparticles are a promising material due to a high surface area that is easily modified and the ability to remove them from blood with an external magnetic field. Plasma protein adsorption and clot formation kinetics were determined for unmodified and albumin-modified iron oxide magnetic nanoparticles. Albumin was selected because it can bind uremic toxins, and it is commonly used to passivate surfaces. Coatings were formed and characterized using transmission electron microscopy, thermogravimetric analysis, and zeta-potential analysis. Clotting kinetics, total protein assays, and immunoblots were used to analyze the effect surface modification has on protein adsorption events. Unmodified nanoparticles showed rapid clotting and more adsorbed protein compared to albumin-coated iron oxide nanoparticles. Immunoblots show that modified particles showed changes in albumin, protein C, Immunoglobulin G, transferrin, fibrinogen, α1-antitrypsin, vitronectin, plasminogen, prothrombin, and antithrombin levels compared to unmodified controls. The hemocompatibility of adsorbent materials is essential to their clinical application in clearing the blood of uremic toxins.
肾衰竭会导致血液中代谢物的积累。这些代谢物的积累与这些患者的死亡率和发病率增加有关;因此,这些代谢物通常被称为尿毒症毒素。一些尿毒症毒素在血液中的保留是由于与血清白蛋白的强烈相互作用,阻止了使用标准血液透析技术清除它们。吸附剂被认为是清除血液中尿毒症毒素的下一代技术,而氧化铁磁性纳米粒子是一种很有前途的材料,因为它具有高表面积,易于修饰,并且可以用外部磁场从血液中去除。测定了未修饰和白蛋白修饰的氧化铁磁性纳米粒子的血浆蛋白吸附和凝血形成动力学。选择白蛋白是因为它可以结合尿毒症毒素,并且通常用于钝化表面。使用透射电子显微镜、热重分析和zeta 电位分析对涂层进行了形成和表征。凝血动力学、总蛋白测定和免疫印迹用于分析表面修饰对蛋白质吸附事件的影响。与白蛋白包覆的氧化铁纳米粒子相比,未修饰的纳米粒子表现出更快的凝血和更多的吸附蛋白。免疫印迹显示,与未修饰的对照相比,改性颗粒的白蛋白、蛋白 C、免疫球蛋白 G、转铁蛋白、纤维蛋白原、α1-抗胰蛋白酶、玻连蛋白、纤溶酶原、凝血酶原和抗凝血酶水平发生了变化。吸附剂材料的血液相容性对其在清除血液中尿毒症毒素方面的临床应用至关重要。