Role of Protein Corona in the Fate of Hydrophilic Polymeric Nanoparticles: A Fundamental Study

纳米颗粒是尺寸在纳米量级的物质颗粒。在生物环境中，纳米颗粒获得一层蛋白质，称为日冕，其日冕的组成对纳米颗粒的生物命运有着至关重要的影响。虽然在过去的十年里，人们已经做了各种研究来了解纳米粒子的蛋白质电晕，但对通常使用的亲水性(即“亲水”)生物聚合物纳米粒子上形成的蛋白质电晕知之甚少。该项目的研究小组将研究针对一些亲水性生物聚合物形成的蛋白质日冕。目的是破译蛋白质冠状结构的组成，并将识别出的蛋白质与纳米颗粒的表面化学相关联。然后，研究人员将利用这一知识进一步了解纳米颗粒的生物命运。这项研究将加深我们对蛋白质电晕的基本了解，确定负责促进或减少细胞摄取的关键蛋白质，并指导设计更好、更安全的纳米颗粒，用于广泛的应用。该研究项目是研究生和本科生进行尖端研究的训练场。研究团队将通过各种校园项目招收本科生，特别是STEM领域代表性不足的学生。这项工作的知识将通过在国际会议上的发言、制定新课程的课程和外联活动来传播。纳米粒子上的蛋白质日冕已被证明是决定纳米粒子生物命运的决定因素。目前，大部分研究都集中在模型疏水聚苯乙烯或无机纳米粒子体系上的电晕形成。人们对最常用的亲水性生物聚合物纳米颗粒上形成的蛋白质电晕知之甚少。这项研究的目标是使用一个定义明确的水凝胶纳米颗粒系统来破译针对一些亲水性生物聚合物形成的蛋白质冠状结构的组成，并将识别出的蛋白质与纳米颗粒的表面化学和命运相关联。磁性纳米粒子将被包裹在水凝胶纳米粒子中，从而能够使用磁场轻松地获取蛋白质电晕。蛋白质冠状结构的组成将使用最先进的蛋白质组学分析进行解码，以深入了解血浆蛋白质与这些亲水性聚合物的相互作用。这些被吸附的蛋白质对纳米粒子命运的影响将通过使用巨噬细胞和树突状细胞的细胞摄取实验来进一步研究。对蛋白质电晕的基本了解将指导设计更好、更安全的纳米粒子，用于广泛的生物医学和工程应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Nanoparticles are particles of matter with dimensions on the order of nanometers. In a biological environment, nanoparticles acquire a layer of proteins, called a corona, and the composition of their corona critically affects the biological fate of nanoparticles. Although a variety of studies have been done to understand the protein corona of nanoparticles over the past decade, little is known about protein corona formed on commonly used hydrophilic (i.e., "water loving") biopolymer nanoparticles. The research team on this project will study the protein corona formed against a number of hydrophilic biopolymers. The objectives are to decode the compositions of the protein coronas and to correlate the identified proteins with the surface chemistry of the nanoparticles. The researchers will then use this knowledge to further understand the biological fate of the nanoparticles. This research will enhance our fundamental understanding of protein corona, identify key proteins responsible for the promotion or reduction of cellular uptake, and guide the design of better and safer nanoparticles for a broad range of applications. The research project serves as a training ground for graduate and undergraduate students to perform cutting edge research. The research team will recruit undergraduate students, particularly students underrepresented in STEM fields, through various on-campus programs. Knowledge from this work will be disseminated through presentations at international conferences, the development of curricula for new courses, and outreach activities. Protein corona on nanoparticles have been shown to be determinant for the biological fate of nanoparticles. At present, most research has focused on corona formation on model hydrophobic polystyrene or inorganic nanoparticle systems. Little is known about protein corona formed on the most commonly used hydrophilic biopolymer nanoparticles. The objectives of this study are to decode the compositions of protein coronas formed against a number of hydrophilic biopolymers using a well-defined, hydrogel nanoparticle system and to correlate the identified proteins with the surface chemistry and fate of nanoparticles. Magnetic nanoparticles will be encapsulated inside the hydrogel nanoparticles to enable the facile harvesting of protein corona using a magnetic field. The compositions of protein coronas will be decoded using state-of-the-art proteomic analysis to provide insights into the interaction of plasma proteins with these hydrophilic polymers. The impact of these adsorbed proteins on the fate of the nanoparticles will be investigated further through cellular uptake experiments using both macrophage and dendritic cells. A fundamental understanding of protein corona will guide the design of better and safer nanoparticles for a wide range of biomedical and engineering applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.