Abstract：
Regardless of the promising use of nanoparticles (NPs) in biomedical applications, several toxic effects have increased the concerns about the safety of these nanomaterials. Although the pathways for NPs toxicity are diverse and dependent upon many parameters such as the nature of the nanoparticle and the biochemical environment, numerous studies have provided evidence that direct contact between NPs and biomolecules or cell membranes leads to cell inactivation or damage and may be a primary mechanism for cytotoxicity. In such a context, this work focused on developing a fast and accurate method to characterize the interaction between NPs, proteins and lipidic membranes by surface plasmon resonance imaging (SPRi) technique. The interaction of gold NPs with mimetic membranes was evaluated by monitoring the variation of reflectivity after several consecutive gold NPs injections on the lipidic membranes prepared on the SPRi biochip. The interaction on the membranes with varied lipidic composition was compared regarding the total surface concentration density of gold NPs adsorbed on them. Then, the interaction of gold and silver NPs with blood proteins was analyzed regarding their kinetic profile of the association/dissociation and dissociation constants (koff). The surface concentration density on the membrane composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine and cholesterol (POPC/cholesterol) was 2.5 times higher than the value found after the injections of gold NPs on POPC only or with dimethyldioctadecylammonium (POPC/DDAB). Regarding the proteins, gold NPs showed preferential binding to fibrinogen resulting in a value of the variation of reflectivity that was 8 times higher than the value found for the other proteins. Differently, silver NPs showed similar interaction on all the tested proteins but with a variation of reflectivity on immunoglobulin G (IgG) 2 times higher than the value found for the other tested proteins.
摘要：
无论纳米粒子（NPs）在生物医学应用中的应用前景如何，一些毒性作用增加了人们对这些纳米材料安全性的担忧。尽管NPs毒性的途径是多种多样的，并且取决于许多参数，例如纳米粒子的性质和生化环境，许多研究提供证据表明，NP与生物分子或细胞膜之间的直接接触会导致细胞失活或损伤，并且可能是细胞毒性的主要机制。在这样的背景下,这项工作的重点是开发一种快速准确的方法来表征NP之间的相互作用，通过表面等离子体共振成像（SPRi）技术研究蛋白质和脂质膜。通过监测在SPRi生物芯片上制备的脂质膜上连续注射几次金NP后反射率的变化来评估金NP与模拟膜的相互作用。关于吸附在其上的金NP的总表面浓度密度，比较了具有不同脂质组成的膜上的相互作用。然后，分析了金和银NP与血液蛋白的缔合/解离和解离常数（koff）的动力学曲线。由1-棕榈酰-2-油酰基-甘油-3-磷酸胆碱和胆固醇（POPC/胆固醇）组成的膜上的表面浓度密度比仅在POPC上注射金NP后发现的值高2.5倍二甲基十八烷基铵（POPC/DDAB）。关于蛋白质，金NP显示与纤维蛋白原的优先结合，导致反射率变化的值比其他蛋白质的值高8倍。不同的是,银NP在所有测试蛋白质上显示相似的相互作用，但在免疫球蛋白G（IgG）上的反射率变化比其他测试蛋白质的反射率高2倍。
