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RUI: Charge Modified Antibody for Robust and Directional Adsorption onto Gold Nanoparticles

RUI：电荷修饰抗体，可牢固、定向吸附到金纳米颗粒上

基本信息

批准号：
1807126
负责人：
Jeremy Driskell
金额：
$ 34.49万
依托单位：
Board of Trustees of Illinois State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807126&HistoricalAwards=false
关键词：
RUI Charge Modified Antibody Robust

项目摘要

The need to protect against biological threats and to develop effective drug therapies requires the development of novel detection strategies. The unique properties of gold nanoparticles (AuNPs) make them candidates for materials used in detection technologies. Critical for the success of emerging detection technologies is the attachment of proteins, i.e., antibodies, onto the surface of the AuNPs. Despite extensive efforts in the area of antibody-AuNP conjugation chemistry, current attachment chemistries are not universally applicable to all antibodies, often diminish the function of the antibody, and result in compounds with limited stability. In an effort to address these challenges and to realize the full potential of AuNP-enabled assays, Dr. Jeremy Driskell and his research group at Illinois State University are investigating the underlying principles of the antibody-AuNP interaction. This research is conducted with the support of the Macromolecular, Supramolecular and Nanochemistry Program. These studies will promote the rational design of highly active and stable antibody-AuNP conjugates. The project provides an intense research experience to undergraduate students who learn advanced analytical techniques and gain an appreciation for a multidisciplinary approach to problem solving. Additionally, Dr. Driskell and his undergraduate students participate in the Illinois Summer Research Academy, an educational outreach program that provides high school students from across the nation with an opportunity to work in a research laboratory. Despite many successful examples of antibody-AuNP conjugates, immobilization chemistry still presents a challenge. Direct adsorption of the antibody onto AuNPs is often effective; however, adsorption conditions vary among proteins in an unpredictable manner and the activity of the conjugate is variable. Dr. Driskell's research seeks to identify the underlying principles that cause some antibodies to adsorb onto AuNPs to form stable, highly active conjugates, while other antibodies adsorb weakly and/or exhibit poor binding activity. Dr. Driskell's lab investigates the adsorption dynamics of antibodies onto AuNPs by measuring the adsorption affinity, orientation, reversibility, and displacement by other proteins. Antibodies are chemically modified to precisely alter the protein charge. A systematic investigation into adsorption elucidates the foundational principles needed to build a predictive model for effective surface modification. These efforts support Dr. Driskell's long-term goal of developing a strategy to immobilize antibodies onto AuNPs to form highly active, oriented, and stable conjugates for use in AuNP-enabled immunoassays.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.

保护免受生物威胁和开发有效药物疗法的需要需要开发新的检测策略。金纳米粒子（AuNPs）的独特性质使其成为检测技术中使用的材料的候选者。新兴检测技术成功的关键是蛋白质的附着，即，抗体，到AuNP的表面上。尽管在抗体-AuNP缀合化学领域中进行了广泛的努力，但目前的连接化学并不普遍适用于所有抗体，经常削弱抗体的功能，并导致化合物具有有限的稳定性。为了应对这些挑战并实现AuNP启用的测定的全部潜力，伊利诺斯州州立大学的Jeremy Driskell博士和他的研究小组正在研究抗体-AuNP相互作用的基本原理。这项研究是在大分子，超分子和纳米化学计划的支持下进行的。这些研究将促进高活性和稳定的抗体-金纳米粒子偶联物的合理设计。该项目提供了一个激烈的研究经验，本科生谁学习先进的分析技术，并获得赞赏的多学科方法来解决问题。Driskell和他的本科生参加了伊利诺伊州夏季研究学院，这是一个教育推广计划，为来自全国各地的高中生提供在研究实验室工作的机会。尽管抗体-AuNP缀合物有许多成功的实例，但固定化化学仍然存在挑战。将抗体直接吸附到AuNP上通常是有效的;然而，吸附条件以不可预测的方式在蛋白质之间变化，并且缀合物的活性是可变的。Driskell博士的研究旨在确定导致一些抗体吸附到AuNP上以形成稳定，高活性缀合物的基本原理，而其他抗体吸附较弱和/或表现出较差的结合活性。Driskell博士的实验室通过测量吸附亲和力、方向、可逆性和其他蛋白质的置换来研究抗体在AuNP上的吸附动力学。抗体经过化学修饰以精确改变蛋白质电荷。对吸附的系统研究阐明了建立有效表面改性的预测模型所需的基本原理。这些努力支持Driskell博士的长期目标，即开发一种策略，将抗体结合到AuNP上，形成高活性、定向和稳定的缀合物，用于AuNP免疫测定。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。