Protein Corona-Induced Modification of Silver Nanoparticle Aggregation in Simulated Gastric Fluid.
Protein Corona-Induced Modification of Silver Nanoparticle Aggregation in Simulated Gastric Fluid.
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DOI：
10.1039/c6en00278a
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发表时间：
2016-12-01
期刊：
影响因子：
--
通讯作者：
Philbert MA
中科院分区：
文献类型：
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作者：
Ault AP;Stark DI;Axson JL;Keeney JN;Maynard AD;Bergin IL;Philbert MA
由于银纳米颗粒广泛掺入一系列生物医学和消费品中，因此银纳米颗粒（AgNPs）的摄入对人类健康造成了相当大的影响。然而，AgNPs在胃肠道胃隔室内的修饰程度仍然知之甚少。研究尚未充分评估AgNPs在胃中最丰富的蛋白质胃蛋白酶等生物大分子存在下的理化变化程度，以及AgNPs对蛋白质结构和活性的影响。在此，将两种不同尺寸和表面涂层（20和110 nm，柠檬酸盐或聚乙烯吡啶酮）的AgNPs添加到模拟胃液（SGF）中，添加或不添加猪胃蛋白酶，ph值分别为2.0,3.5和5.0，代表餐前（禁食）和餐后（喂食）条件之间的范围。所有AgNPs的直径都迅速增加，在胃蛋白酶存在时直径增加更大，这表明胃蛋白酶促进了AgNPs的聚集。AgNPs与胃蛋白酶的相互作用仅能最小程度地降低蛋白质的蛋白水解功能能力，两种涂层的较小颗粒（20 nm）的抑制作用最大。在不同的AgNPs中，即使在高颗粒浓度下，也没有观察到胃蛋白酶二级结构元素的变化。这项研究强调了纳米颗粒聚集或溶解与胃肠道中蛋白质等生物元素相互作用的大小依赖动力学。此外，这些结果表明，除了质量之外，了解纳米颗粒的化学形态和聚集状态在评估体内纳米颗粒暴露的毒理学效应时至关重要。
Due to their widespread incorporation into a range of biomedical and consumer products, the ingestion of silver nanoparticles (AgNPs) is of considerable concern to human health. However, the extent to which AgNPs will be modified within the gastric compartment of the gastrointestinal tract is still poorly understood. Studies have yet to fully evaluate the extent of physicochemical changes to AgNPs in the presence of biological macromolecules, such as pepsin, the most abundant protein in the stomach, or the influence of AgNPs on protein structure and activity. Herein, AgNPs of two different sizes and surface coatings (20 and 110 nm, citrate or polyvinylpyrrolidone) were added to simulated gastric fluid (SGF) with or without porcine pepsin at three pHs (2.0, 3.5, and 5.0), representing a range of values between preprandial (fasted) and postprandial (fed) conditions. Rapid increases in diameter were observed for all AgNPs, with a greater increase in diameter in the presence of pepsin, indicating that pepsin facilitated AgNPs aggregation. AgNPs interaction with pepsin only minimally reduced the protein’s proteolytic functioning capability, with the greatest inhibitory effect caused by smaller (20 nm) particles of both coatings. No changes in pepsin secondary structural elements were observed for the different AgNPs, even at high particle concentrations. This research highlights the size-dependent kinetics of nanoparticle aggregation or dissolution from interaction with biological elements such as proteins in the gastrointestinal tract. Further, these results demonstrate that, in addition to mass, knowing the chemical form and aggregation state of nanoparticles is critical when evaluating toxicological effects from nanoparticle exposure in the body.