School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.
Nat Nanotechnol. 2011 Jan;6(1):39-44. doi: 10.1038/nnano.2010.250. Epub 2010 Dec 19.
The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.
纳米颗粒的化学成分、尺寸、形状和表面特性影响蛋白质与这些颗粒结合的方式，而这反过来又影响纳米颗粒与细胞和组织相互作用的方式。与蛋白质结合的纳米材料可能导致生理和病理变化，包括巨噬细胞摄取、血液凝固、蛋白质聚集和补体激活，但导致这些变化的机制仍知之甚少。在这里，我们表明带负电荷的聚（丙烯酸）-接枝金纳米颗粒与纤维蛋白原结合并诱导其展开，从而促进与整合素受体 Mac-1 的相互作用。该受体的激活增加了 NF-κB 信号通路，导致炎症细胞因子的释放。然而，并非所有与纤维蛋白原结合的纳米颗粒都表现出这种效应。我们的结果表明，某些纳米颗粒与血浆中纤维蛋白原的结合为炎症反应中更常见的氧化应激在纳米材料中的作用提供了一种替代机制。
