Nanoparticle-Protein Corona Structural Changes and Immunoreactivity

描述(申请人提供)：工程纳米材料具有独特的电学、机械和物理化学性质，有可能对我们社会的许多方面产生影响。然而，纳米材料的健康和安全最近已成为公众以及政策制定者和资助机构的主要关切。考虑到纳米材料在食品、化妆品、医药、建筑、生物成像方面的巨大潜力，以及在制造或研究使用过程中可能暴露的风险，这种担忧是合理的。最近发现，纳米材料在进入生理环境后，会与蛋白质、多肽、脂质和氨基酸发生物理吸附，形成蛋白质“日冕”，从而在细胞、组织和整个生物体水平上影响纳米材料在宿主系统内的生物利用度和分布。因此，对纳米材料的健康和安全影响的研究必须解决以下两个关键问题：1)蛋白质结合动力学和它们与纳米颗粒相互作用引起的构象变化；2)细胞受体识别蛋白质电晕以及随后对纳米材料和改变的蛋白质结构的免疫反应。该项目的中心假设是，纳米材料和“日冕”成分之间的物理化学作用会导致蛋白质构象的变化，从而导致巨噬细胞和树突状细胞的激活以及差异性抗原的呈递。我们将通过以下方法验证这一假设：1)表征一组纳米颗粒蛋白冠状；2)测定体外 纳米蛋白冠层的细胞和免疫命运。了解纳米材料蛋白质电晕对免疫应答的影响对于发展安全的纳米技术至关重要。

DESCRIPTION (provided by applicant): Engineered nanomaterial's have unique electrical, mechanical and physicochemical properties with potential to impact many facets of our society. However, the health and safety of nanomaterial's has recently become a major concern to the public as well as to policy makers and funding agencies. Such concern is justified in light of the vast potential for nanomaterial use in food, cosmetics, medicine, construction, bioimaging, as well as the potential exposures during manufacturing or research use. It has recently been established that nanomaterials, upon entry into a physiological environment, exhibit a tendency of physical adsorption with proteins, peptides, lipids and amino acids to render a protein "corona" that may influence the bioavailability and distribution of nanomaterials within the host system, at the cellular, tissue and whole organism level. Consequently, research on the health and safety implications of nanomaterials must address the following two key questions: 1) protein binding kinetics and conformational change resulting from their interaction with the nanoparticle, 2) recognition of protein corona by cellular receptors and subsequent immune responses to both the nanomaterial and the altered protein structure. The central hypothesis of this project is that the physicochemical interactions between nanomaterials and the "corona" components leads to changes in protein conformation, which will subsequently result in macrophage and dendritic cell activation and differential antigen presentation. We will test this hypothesis by: 1) characterizing a set of nanoparticle protein coronas; 2) determining the in vitro cellular and immune fate of nanoparticle protein corona. Understanding the impact of nanomaterial protein corona on immune response will be crucial for the development of safe nanotechnologies.