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：Hogan在一个基本层面上，纳米医学，其中定制的纳米颗粒被用于治疗或诊断疾病，以及纳米毒理学，其中纳米颗粒的健康影响令人担忧，研究纳米颗粒与人体内生物分子结构之间的相互作用，特别是与蛋白质的相互作用。在这两个领域都有相当大的兴趣是调理作用的过程，在这个过程中，血液蛋白与纳米颗粒结合，最终导致体内的免疫反应。在基础水平上发展纳米医学和纳米毒理学的一个主要障碍是缺乏可用于纳米颗粒的分析技术，从这些分析技术可以推断与其与生物系统相互作用相关的纳米颗粒特性。明尼苏达大学的研究团队将与TSI公司的一个团队合作，开发两个专门设计的新测量系统，以检查选定的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，特别是电喷雾气溶胶发生器，将体外模型系统中的纳米颗粒-蛋白质复合体雾化，从而能够使用差分迁移率分析仪(DMA)和凝聚颗粒计数器测量其尺寸分布。在第一个拟议的系统中，将开发一个电感耦合质谱仪，并用于确定蛋白质纳米颗粒复合体中无机纳米颗粒核心的大小，允许根据纳米颗粒大小和化学组成推断结合到纳米颗粒上的蛋白质数量。在第二个系统中，将使用新开发的微型颗粒入液采样器和电喷雾质谱仪，通过氢-氚交换来分析DMA大小分类的纳米颗粒-蛋白质复合体。该系统将允许确定蛋白质上发生与纳米颗粒结合的位置，这是现有仪器无法实现的。当这两个新系统一起使用时，这两个新系统将允许一种专门针对纳米医学和纳米毒理学的纳米颗粒表征的新方法，从而允许在这些领域以及纳米颗粒科学和工程中进行变革性研究。开发下一代医学技术的一个关键问题是提高我们对纳米材料如何与生命的基本构件，即蛋白质相互作用的理解。为了解决这个问题，学术界和工业界的研究人员之间需要新的测量技术和合作努力。明尼苏达大学的霍根和比肖夫教授与TSI公司的法默博士合作，计划开发两种变革性的测量系统，专门用于监测蛋白质和纳米材料之间的相互作用。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性质，从而促进它们与生物分子的相互作用，以及类似地，体内哪些分子与纳米材料相互作用。合作研究活动将包括明尼苏达大学的学生和教职员工以及TSI公司的工作人员科学家。拟议的活动不仅将导致开发两个可供广泛分布的测量系统，而且还将在分子水平上对纳米颗粒与生物系统之间的相互作用进行新的测量。