Nanoparticle-Protein Corona Structural Changes and Immunoreactivity

纳米颗粒-蛋白质电晕结构变化和免疫反应性

• 批准号: 8769110
• 负责人: Jared Michael Brown
• 金额: $ 8.95万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769110
• 关键词: Address; Adsorption; Affinity; Amino Acids; Antigen Presentation; Antigen-Presenting Cells; Antigens; Binding; Biological Availability; Biological Markers; Biophysics; Blood coagulation; CD4 Positive T Lymphocytes; Capsid Proteins; Carbon; Carbon Nanotubes; Cells; Characteristics; Circular Dichroism Spectroscopy; Complement Activation; Cosmetics; Data; Dendritic Cells; Dendritic cell activation; Development; Disease; Engineering; Environment; Exhibits; Fatty Acids; Fibrinogen; Food; Fourier Transform; Funding Agency; Health; Histocompatibility Antigens Class II; ITGAM gene; Immune; Immune response; Immunology; In Vitro; Inflammatory; Kinetics; Libraries; Light; Lipids; Macrophage Activation; Mechanics; Medicine; Mission; Modeling; Morphology; Nanostructures; Nanotechnology; National Institute of Environmental Health Sciences; Ovalbumin; Pathogenesis; Peptides; Physiological; Policy Maker; Process; Production; Property; Protein Binding; Protein Conformation; Proteins; Proteolysis; Reporting; Research; Role; Safety; Science; Serum Albumin; Shapes; Societies; Structural Protein; Surface; System; T-Cell Receptor; T-Lymphocyte; TLR4 gene; Technology; Testing; Tissues; Toxicology; Transgenic Organisms; Variant; Whole Organism; base; bioimaging; cell type; chemical reaction; cytokine; cytotoxicity; immunoreactivity; improved; macrophage; nanomaterials; nanoparticle; nanotoxicity; novel; protein aggregation; protein structure; public health relevance; receptor; scavenger receptor; uptake

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.

描述（由申请人提供）：工程纳米材料具有独特的电气，机械和物理化学特性，有可能影响我们社会的许多方面。然而，纳米材料的健康和安全性最近已成为公众以及政策制定者和资助机构的主要关注点。鉴于纳米材料在食品、化妆品、医药、建筑、生物成像中的巨大潜力，以及在制造或研究使用过程中的潜在暴露，这种担忧是合理的。最近已经确定，纳米材料在进入生理环境后，表现出与蛋白质、肽、脂质和氨基酸物理吸附的趋势，以使蛋白质“冠”，这可能影响纳米材料在宿主系统内在细胞、组织和整个生物体水平上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与纳米颗粒相互作用引起的构象变化，2）细胞受体对蛋白质冠的识别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“冠”成分之间的物理化学相互作用导致蛋白质构象的变化，随后导致巨噬细胞和树突状细胞活化和差异抗原呈递。我们将通过以下方式来检验这一假设：1）表征一组纳米颗粒蛋白质冠状体; 2）测定体外细胞培养物中的蛋白质冠状体。 纳米颗粒蛋白质冠的细胞和免疫命运。了解纳米材料蛋白质冠对免疫反应的影响对于开发安全的纳米技术至关重要。