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.

1133285hghan在基本层面上，纳米医学（使用特制的纳米颗粒治疗或诊断疾病）和纳米毒理学（关注纳米颗粒对健康的影响）研究纳米颗粒与人体内生物分子结构之间的相互作用，特别是与蛋白质之间的相互作用。在这两个领域中，颇受关注的是调理过程，即血液蛋白与纳米颗粒结合，最终在体内产生免疫反应。纳米医学和纳米毒理学在基础水平上发展的一个主要障碍是缺乏可用的纳米颗粒分析技术，从这些技术中可以推断出纳米颗粒与生物系统相互作用相关的特性。明尼苏达大学的研究小组与TSI公司的一个研究小组合作，将开发两种新的测量系统，专门用于检测所选蛋白质与无机纳米颗粒的结合。这两个系统都将使用气溶胶测量仪器，特别是电喷雾气溶胶发生器，从体外模型系统中雾化纳米颗粒-蛋白质复合物，允许使用差分迁移率分析仪（DMA）和冷凝颗粒计数器测量其尺寸分布。在第一个提出的系统中，将开发一个电感耦合质谱仪，用于确定蛋白质纳米颗粒复合物内无机纳米颗粒核心的大小，从而推断与纳米颗粒结合的蛋白质数量作为纳米颗粒大小和化学成分的函数。在第二个系统中，将使用新开发的微粒-液体进样器和电喷雾质谱法，通过氢-氘交换分析DMA大小分类的纳米颗粒-蛋白质复合物。该系统将允许确定蛋白质上与纳米颗粒发生结合的位点，这是现有仪器无法做到的。当串联使用时，这两种新系统将为纳米医学和纳米毒理学提供一种新的纳米颗粒表征方法，使这些领域以及纳米颗粒科学和工程的变革性研究成为可能。开发下一代医疗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组成部分（即蛋白质）相互作用的理解。为了解决这个问题，新的测量技术和学术界和工业界研究人员之间的合作努力将是必要的。明尼苏达大学的Hogan和Bischof教授与TSI公司的Farmer博士合作，计划开发两种革命性的测量系统，专门用于监测蛋白质和纳米材料之间的相互作用。这两种测量系统将使科学家、工程师和医生第一次能够确定特定纳米材料的精确特性，从而促进它们与生物分子的相互作用，同样地，也可以确定体内哪些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师以及TSI公司的科学家。所提出的活动不仅将导致两种广泛分布的测量系统的发展，而且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。