CAREER: Harnessing continuous growth mechanism to synthesize water-soluble magnetic nanoparticles for magnetic particle imaging

非技术摘要：这项由材料研究部生物材料计划支持的职业奖项旨在了解水溶性磁性纳米颗粒(MNPs)的持续生长机制，并利用该生长机制合成用于磁性粒子成像(MPI)应用的MNPs。该项目通过促进科学进步和促进公众健康来服务于国家利益。MPI是一种很有前途的新型成像方式，因为它可以直接从MNPs中产生正对比信号，而不需要使用有害的电离辐射。MPI具有无限制的组织穿透深度、低背景信号和高灵敏度。然而，MPI目前还不能用于临床应用。一个主要障碍是缺乏MPI特异性的MNPs作为示踪剂。高性能的MNPs对于实现MPI在临床翻译中的潜力至关重要。这个项目的灵感来自赵永峰教授的初步研究，他证明了水溶性MNPs可以以连续生长的方式合成。所得到的MNPs表现出高的MPI性能。然而，其持续生长的机制尚不清楚，水溶性MNPs与MPI性能之间的相关性尚未建立。解决这些问题将加速MPI用高性能MNPs的设计、合成和制造。通过该项目获得的知识将促进水溶性MNPs的受控合成，并为MPI在医疗保健中的应用扫清障碍。该项目将把拟议的研究活动与教育计划结合起来，以培训未被充分代表的学生获得高级学位。该推广计划是在密西西比州国家科学博物馆举行的年度科学创造者活动期间向公众传播研究成果。技术综述：本提案的首要目标是从分子水平全面了解水溶性磁性纳米颗粒(MNPs)在多元醇中的连续生长机理，旨在提高MNPs的磁性粒子成像(MPI)性能。这项研究项目是有意义的，因为MPI是一种新兴的示踪剂成像方式，可以克服现有成像技术的许多局限性。MNPs的性质决定了它们的灵敏度和分辨率，这对于MPI的进一步应用是必不可少的。为了实现这一总体目标，本项目旨在1)探索控制合成水溶性MNPs的连续生长机理；2)揭示MNPs在多元醇中的生长规律；3)控制合成水溶性MNPs的反应参数；4)拓展合成水溶性MNPs的机理；5)研究在多元醇中合成的MNPs的MPI性质。该项目将加速MPI用高性能MNPs的选择、合成和制造。教育计划是将这一研究项目与一项教育倡议相结合，该教育倡议旨在系统地培训杰克逊州立大学(JSU)STEM领域的少数族裔本科生以获得高级学位。该项目将与JSU通过布鲁克海文国家实验室(BNL)提供的课程相结合。联合州立大学的学生将与来自BNL的研究科学家互动，并学习最先进的材料表征技术。这项研究将作为“你是化学家”比赛的一部分，帮助培养和提高中学生对STEM的热情。该项目由生物材料计划和既定的刺激竞争研究计划(EPSCoR)联合资助。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。

Non-technical summary: This CAREER award supported by the Biomaterials program in the Division of Materials Research aims to understand the continuous growth mechanism of water-soluble magnetic nanoparticles (MNPs) and harness the growth mechanism to synthesize MNPs for magnetic particles imaging (MPI) application. The project serves the national interest by promoting the progress of science and advancing public health. The MPI is a promising and novel imaging modality because it can generate positive contrast signals directly from MNPs without using harmful ionizing radiation. The MPI has unlimited tissue penetration depth, low background signals, and high sensitivity. Nevertheless, the MPI is currently not available for clinical applications. One major obstacle is a lack of MPI-specific MNPs as tracers. High-performance MNPs are critical to materialize the potential of MPI in clinical translation. This project is inspired by Professor Yongfeng Zhao’s pilot study demonstrating that water-soluble MNPs can be synthesized in a continuous growth manner. The resulting MNPs show high MPI performance. However, the mechanism of the continuous growth is still unknown, and the correlation between water-soluble MNPs and MPI performance is not established. Addressing these questions will accelerate the design, synthesis, and manufacturing of high-performance MNPs for MPI. The knowledge obtained from this project will stimulate the controlled synthesis of water-soluble MNPs and clear the roadblock for the application of MPI in healthcare. This project will integrate the proposed research activities with education plans to train underrepresented students for advanced degrees. The outreach plan is to disseminate the research findings to the general public during the annual Science Maker event in the Mississippi Museum of National Science. Technical summary:The overarching goal of this proposal is to obtain a holistic molecule-level understanding of the continuous growth mechanism of water-soluble magnetic nanoparticles (MNPs) in polyols, aimed to enhance magnetic particles imaging (MPI) performance of MNPs. The research project is meaningful because MPI is an emerging tracer imaging modality that can overcome many limitations of existing imaging techniques. The properties of MNPs dictate their sensitivity and resolution, which are essential for the further application of MPI. To achieve this overarching goal, this project is designed to 1) explore the continuous growth mechanism for controlled synthesis of water-soluble MNPs; 2) unravel a living growth profile of MNPs in polyols; 3) manipulate the reaction parameters for the synthesis of water-soluble MNPs; 4) expand the mechanism to synthesize water-soluble MNPs with dopants; and 5) study the MPI properties of MNPs synthesized in polyols. This project will accelerate the selection, synthesis, and manufacturing of high-performance MNPs for MPI. The education plan is to integrate this research project with an education initiative that is designed to systematically train minority undergraduate students in the STEM area at Jackson State University (JSU) to obtain advanced degrees. The project will be integrated with a course offered at JSU through the Brookhaven National Laboratory (BNL). JSU students will interact with research scientists from BNL and learn state-of-the-art technologies on materials characterization. This research will be presented as part of the “You Be The Chemist” competition and help foster and enhance the passion for STEM among middle school students.This project is jointly funded by the Biomaterials program and the Established Program to Stimulate Competitive Research (EPSCoR).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.