CAREER: Elucidating the Mechanism of Ionic Liquid-Coated Nanoparticle Interactions with Blood Components

了解纳米材料如何与人体相互作用是安全有效地将其用于医学的关键一步。当纳米粒子被注入血液时，它们会遇到一个丰富的环境，里面充满了各种细胞和蛋白质。密西西比大学的伊登·坦纳博士和她的团队开发了一种离子液体纳米颗粒涂层技术，该技术可以选择性地将纳米颗粒“搭便车”到不同类型的血细胞上。这个职业项目将研究这种现象，以了解这种搭便车的原因和方式，它对细胞膜有什么影响，并测量纳米颗粒和细胞膜之间的力的强度。这项研究项目将提供有关带电材料与血液成分相互作用的关键基础知识。在坦纳博士和她的实验室的支持下，学生参与者将从越来越多的少数人获得研究生教育的机会中招募，科学新星计划。这些来自密西西比州的非裔美国本科生从大学的第一天到毕业及以后都将得到密集的指导和支持，为他们进入研究生院和成为科学领袖做好准备。参与者将与PI合作，返回他们的高中开展外展活动，从而创建一个强大的、支持性的科学家渠道，并最终使科学工作队伍多样化。这一职业计划的研究目标是询问离子液体包裹的纳米颗粒与血液成分之间的相互作用。密西西比大学坦纳实验室已经证明，用胆碱羧酸为基础的离子液体成功地对聚(乳酸-乙醇酸共聚)纳米粒子进行表面修饰，可以使离子液体-纳米粒子优先黏附于全血中的不同血液成分。一项关键的创新将是确定离子液体-聚合物纳米颗粒复合材料在血细胞表面的黏附动力学和机制。该项目将包括以下三个目标：深入了解离子液体-纳米颗粒与细胞膜之间的附着机制(目标1)，评估搭便车对细胞膜的影响(目标2)，以及测量吸引力的强度和搭便车对附着到血管壁的影响(目标3)。PI将使用一系列分析技术来实现这些目标，包括分子动力学模拟、光学镊子、液相色谱-质谱仪和小角X射线散射。这一职业计划的教育目标是建立不断增加的少数族裔获得研究生教育的机会正在崛起的科学之星计划，这是一个密集的指导计划，让密西西比州的非裔美国人科学技术工程和数学学生从大学第一天到最后一天都沉浸在研究中(每年3名参与者，共15名)。该项目与现有的国家科学基金会资助的增加少数人获得研究生教育的机会计划合作，该项目的教育方法将为冉冉升起的科学之星学者提供高度的社会、财政和学术支持，为他们进入研究生院和科学生涯铺平道路。PI将与参与者合作，回到他们的高中开展外展活动。这一奖项反映了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。

Understanding how nanomaterials interact with the human body is a critical step to their safe and effective use in medicine. When nanoparticles are injected into the bloodstream, they encounter a rich environment, replete with diverse kinds of cells and proteins. Dr. Eden Tanner and her team at the University of Mississippi have developed an ionic liquid nanoparticle coating technology which enables selective in situ “hitchhiking” of nanoparticles onto different kinds of blood cells. This CAREER project will investigate this phenomenon to understand why and how this hitchhiking occurs, what impact it has on the cell membranes, and measure the strength of the forces between the nanoparticle and the cell membrane. This research project will provide critical fundamental knowledge on the interaction of charged materials with components of the bloodstream. Supported by Dr. Tanner and her lab, the student participants will be recruited from the Increasing Minority Access to Graduate Education Rising Science Star Program. These cohorts of Mississippi-based African American undergraduate scholars will be intensively mentored and supported from their first day of college until graduation and beyond, preparing them to enter graduate school and for careers as scientific leaders. Participants will work with the PI to return to their high schools to deliver outreach activities, thereby creating a robust, supportive pipeline of scientists and ultimately diversifying the scientific workforce.The research objective of this CAREER program is to interrogate the interactions between ionic liquid-coated nanoparticles and blood components. The Tanner lab at the University of Mississippi has demonstrated that successful surface modification of poly(lactic-co-glycolic) acid nanoparticles with a choline carboxylic acid-based ionic liquid results in preferential adhesion of the ionic liquid-nanoparticles to different blood components in whole blood. A key innovation will be determining the dynamics and mechanisms of adhesion of the ionic liquid-polymeric nanoparticle composites onto blood cell surfaces. The project will consist of the following three objectives: advance knowledge on the mechanism of attachment between the ionic liquid-nanoparticles and the cell membrane (Objective 1), assess the impact of the hitchhiking on the cell membrane (Objective 2), and measure the strength of the attractive forces and the effect of hitchhiking on adhesion to the blood vessel wall (Objective 3). The PI will use a host of analytical techniques to accomplish these objectives, including molecular dynamics simulations, optical tweezers, liquid chromatography-mass spectrometry, and small angle X-ray scattering. The educational objective of this CAREER program is the establishment of the Increasing Minority Access to Graduate Education Rising Science Star Program, an intensive mentoring program that immerses cohorts of Mississippi’s African American Science Technology Engineering and Mathematics students in research from their first day of college until their last (3 participants a year, 15 total). Partnering with the existing National Science Foundation-funded Increasing Minority Access to Graduate Education program, the project’s educational approach will provide the Rising Science Star Scholars with a high degree of social, financial and academic support, paving their path to graduate school and a scientific career. The PI will work in partnership with the participants to travel back to their high schools to conduct outreach activities.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.