GOALI: Fundamental Studies of Nanoparticle-Protein Binding

目标：纳米颗粒-蛋白质结合的基础研究

• 批准号: 1133285
• 负责人: Christopher Hogan
• 金额: $ 32.96万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1133285&HistoricalAwards=false
• 关键词: GOALI; Fundamental; Studies; Nanoparticle; Protein

1133285PI: HoganAt a fundamental level, nanomedicine, in which in which tailor-made nanoparticles are used to treat or diagnose disease, and nanotoxicology, in which the health effects of nanoparticles are of concern, examine the interaction between nanoparticles and biomolecular structures within the human body, in particular with proteins. Of considerable interest in both fields is the process of opsonization, in which blood proteins bind to nanoparticles, eventually resulting in an immunological response within the body. A major roadblock to development in nanomedicine and nanotoxicology at the fundamental level is the dearth of analysis techniques available for nanoparticles from which nanoparticle properties relevant to their interactions with biological systems can be inferred. The research team at the University of Minnesota in collaboration with a team at TSI Incorporate will develop two new measurement systems specifically designed to examine the binding of chosen proteins to inorganic nanoparticles. Both systems will make use of aerosol measurement instrumentation, specifically, an electrospray aerosol generator to aerosolize nanoparticle-protein complexes from an in-vitro model system, allowing for measurement of their size distribution with a differential mobility analyzer (DMA) and condensation particle counter. In the first proposed system, an inductively coupled mass spectrometer will be developed and used to determine the size of the inorganic nanoparticle core within the protein nanoparticle complexes, allowing for inference of the number of proteins bound to nanoparticles as a function of nanoparticle size and chemical composition. In the second system, DMA size classified nanoparticle-protein complexes will be analyzed by hydrogen-deuterium exchange, using a newly developed micro-Particle-into-Liquid Sampler and electrospray mass spectrometry. This system will allow for determination of the site on a protein where binding to nanoparticles occurs, which is not possible with available instrumentation. When used in tandem, these two new systems will allow for a new method of nanoparticle characterization specific for nanomedicine and nanotoxicology, allowing for transformative research in these fields as well as in nanoparticle science and engineering.A key issue in developing next generation medical technologies is improving our understanding of how nanomaterials interact with the basic building blocks of life, namely, proteins. To address this issue, new measurement technologies and collaborative efforts between researchers in academia and in industry will be necessary. Professors Hogan and Bischof of the University of Minnesota, in collaboration with Dr. Farmer of TSI Incorporated plan to develop two transformative measurement systems designed specifically to monitor the interactions between proteins and nanomaterials. These two measurement systems will enable scientists, engineers, and physicians to determine, for the first time, the precise properties of specific nanomaterials which facilitate their interactions with biological molecules, and similarly, which molecules within the body interact with nanomaterials. The collaborative research activities will involve students and faculty at the University of Minnesota as well as staff scientists at TSI Incorporated. The proposed activities will result not only in the development of two measurement systems available for wide distribution, but also new measurements of the interactions between nanoparticles and biological systems at the molecular level.

1133285PI：Hoganat是纳米医学的基本水平，其中使用量身定制的纳米颗粒来治疗或诊断疾病和纳米毒理学，其中纳米颗粒的健康作用引起了关注，研究纳米颗粒和生物分子结构之间的互动蛋白质与蛋白质中的互动，尤其是蛋白质的互动。 在这两个领域的浓厚兴趣是调理过程，其中血蛋白与纳米颗粒结合，最终导致体内的免疫反应。 基本水平上纳米医学和纳米毒理学发展的主要障碍是纳米颗粒可用的分析技术的缺乏，可以推断出与其与生物系统相互作用相关的纳米颗粒特性。明尼苏达大学与TSI Incorparate的团队合作的研究团队将开发两个新的测量系统，专门设计用于检查所选蛋白质与无机纳米颗粒的结合。 这两个系统都将利用气溶胶测量仪器，特别是电喷雾器发电机，以使纳米颗粒 - 蛋白质复合物从体外模型系统中播出纳米颗粒 - 蛋白质复合物，从而可以使用差异迁移率分析仪（DMA）和凝聚力粒子柜台来测量其尺寸分布。在第一个提出的系统中，将开发一个电感耦合的质谱仪并用于确定蛋白质纳米颗粒复合物中无机纳米颗粒核的大小，从而可以将与纳米颗粒结合的蛋白质数量推断为纳米粒子大小和化学成分的函数。 在第二个系统中，DMA大小分类的纳米颗粒 - 蛋白质复合物将通过氢 - 偏见交换分析，使用新开发的微颗粒 - 液体液体采样器和电喷雾质谱法。 该系统将允许在发生与纳米颗粒结合的蛋白质上确定位点，这是在可用的仪器中不可能的。 When used in tandem, these two new systems will allow for a new method of nanoparticle characterization specific for nanomedicine and nanotoxicology, allowing for transformative research in these fields as well as in nanoparticle science and engineering.A key issue in developing next generation medical technologies is improving our understanding of how nanomaterials interact with the basic building blocks of life, namely, proteins. 为了解决这个问题，必须有必要进行新的测量技术和学术界和行业之间的合作工作。 明尼苏达大学的Hogan和Bischof教授与TSI Incorporated计划的Farmer博士合作开发了两种专门监测蛋白质与纳米材料之间相互作用的变革性测量系统。 这两个测量系统将使科学家，工程师和医生能够首次确定特定纳米材料的精确特性，这些特性促进了它们与生物分子的相互作用，类似地，该分子与人体内部的分子与纳米材料相互作用。 合作研究活动将涉及明尼苏达大学的学生和教职员工以及TSI Incorporated的员工科学家。 所提出的活动不仅将导致两个可用于广泛分布的测量系统的开发，而且还会导致分子水平上纳米颗粒与生物系统之间相互作用的新测量。