Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
ACS Chem Neurosci. 2013 Mar 20;4(3):475-85. doi: 10.1021/cn300196n. Epub 2013 Jan 23.
Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer's, a comprehensive understanding of their interactions with Aβ and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of Aβ in aqueous solution. A size and surface area dependent "dual" effect on Aβ fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of Aβ fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation.
超顺磁氧化铁纳米粒子（SPIONs）由于其生物相容性、独特的磁性能以及作为多模态对比剂的应用，被认为是有前途的纳米诊断材料。由于涂覆的 SPIONs 有可能用于诊断和治疗各种脑疾病，如阿尔茨海默病，因此在将其临床应用之前，必须充分了解它们与 Aβ 和其他淀粉样蛋白的相互作用。在这里，我们展示了 SPIONs 涂层的厚度和表面电荷对其在水溶液中 Aβ 纤化动力学的影响。观察到了大小和表面积的“双重”作用。虽然较低浓度的 SPIONs 抑制了纤化，但较高浓度的 SPIONs 则增加了 Aβ 的纤化速率。关于涂层电荷，显然带正电荷的 SPIONs 能够在比带负电荷或不带电荷的 SPIONs 低得多的粒子浓度下促进纤化。这表明，除了存在影响溶液中单体蛋白浓度（从而影响成核时间）的颗粒外，还有结合对蛋白构象的影响。
