Single-Particle Characterization of Nanoparticle Bioconjugates

纳米粒子在生物医学技术中发挥着多种作用，包括作为成像造影剂、热 作为光热疗法的来源，以及作为药物输送载体。在许多这样的应用中，纳米颗粒 使用特定抗体进行功能化，以达到靶向目的。理想情况下，抗体应该分布在 均匀地分布在制剂中的纳米颗粒中，并均匀分布在每个纳米颗粒的表面； 然而，这是一幅过于简单化的图景。在现实中，可能会有不同的数量 每个纳米颗粒的抗体，它们在表面上的空间分布，以及它们的 功能被保留。 为了表征纳米生物结合物，并设计改进的生物结合物， 必须更好地理解表面功能化。以下两个目标将为实现这一目标铺平道路 进球。(1)纳米颗粒制剂内每个纳米颗粒的抗体数量的分布将 使用微孔阵列分析在单颗粒水平上测量金和聚苯乙烯 纳米粒子。(2)抗体在单个纳米颗粒表面的空间排列将是 使用亚衍射限制荧光显微镜成像。将优化制备方法，以 根据纳米粒子的数量和空间分布，生产具有统一功能的纳米粒子 表面上的分子。表面功能化的表征和优化是表面功能化研究的重要内容 基于纳米颗粒的疗法的发展。提高抗体的均一性和质量 功能化将导致目标定位的改进。 该项目将在德克萨斯大学物理和天文学系进行 圣安东尼奥，这是全国最大的指定拉美裔服务机构之一。一个重要的部分 该计分项目将培训来自历史上代表性不足的群体的博士生 物理和健康科学，以及在这个不断发展的机构的研究水平的提升。

Nanoparticles play several roles in biomedical technology, including as imaging contrast agents, heat sources for photothermal therapy, and as drug delivery vehicles. In many of these applications, nanoparticles are functionalized with specific antibodies for targeting purposes. Ideally, antibodies would be distributed equally among the nanoparticles in a preparation and evenly distributed on each nanoparticle’s surface; however, this is an overly simplistic picture. In reality, there are likely to be variations in the number of antibodies per nanoparticle, their spatial distribution on the surface, and the degree to which their function is preserved. In order to characterize nanoparticle bioconjugates, and to design improved ones, the details of the surface functionalization must be better understood. The following two aims will pave the way towards this goal. (1) The distributions of the number of antibodies per nanoparticle within a nanoparticle preparation will be measured at the single-particle level using microwell array analysis, for both gold and polystyrene nanoparticles. (2) The spatial arrangement of antibodies on the surfaces of individual nanoparticles will be imaged using sub-diffraction-limited fluorescence microscopy. The preparation methods will be optimized to produce nanoparticles with uniform functionalization in terms of the number and spatial distribution of molecules on the surface. Characterizing and optimizing the surface functionalization is important for the development of nanoparticle-based therapies. Improving the uniformity and quality of antibody functionalization will lead to improved targeting. The project will be carried out in the Department of Physics and Astronomy at the University of Texas at San Antonio, which is one of the country’s largest designated Hispanic Serving Institutions. An important part of this SCORE project will be the training of Ph.D. students from groups historically underrepresented in the physical and health sciences, and the elevation of research at this growing institution.