Excellence in Research: Direct synthesis of water soluble iron oxide nanoparticles with high relaxivity and interaction with small molecules

非技术总结：该项目研究了磁共振成像（MRI）信号如何随着氧化铁纳米颗粒与生物活性分子相互作用而变化。对这种信号变化的理解为使用MRI监测药物递送和释放提供了科学基础，这将显着改善癌症等疾病的治疗，因为药物的剂量和频率可以根据实时药物摄取信息进行调整。当前用于监测药物递送的方法的主要挑战包括缺乏高灵敏度和待成像的有限组织体积。我们通过合成高水溶性氧化铁纳米颗粒并将其用作MRI试剂来克服这些挑战。MRI是临床实践中一种强大的成像技术，因为它以非侵入性、全身和实时监测的方式提供具有出色细节的图像。纳米颗粒的多功能特性为在成像的辅助下精确递送治疗剂提供了独特的优势。该项目的广泛影响将通过以下方式实现：（1）向科学界传播从本研究中获得的知识，以监测非侵入性监测器极其重要的药物输送;（2）为本科生和研究生提供尖端研究机会，特别是那些来自杰克逊州立大学（JSU）代表性不足的学生;（3）在密西西比自然科学博物馆举办的“密西西比科学制造者”活动期间，通过展览推广STEM教育。技术总结：纳米颗粒可以通过改变药代动力学来提高药物疗效和降低毒性。为了跟踪药物的递送行为，通常附加荧光标记或放射性示踪剂。然而，荧光标记的固有缺点在于光的组织穿透的限制。可用性是放射性示踪剂方法的一个重大挑战。相比之下，氧化铁纳米颗粒（IONP）可以用作自报告的药物递送系统，因为它们能够改变组织中的水弛豫率和它们优异的生物相容性。尽管人们对超小氧化铁纳米颗粒（ESIONP）的T1加权磁特性有着浓厚的兴趣，但生物活性分子的影响尚未得到研究。此外，IONP的T1弛豫性能相对较低。部分原因是现有方法合成的单分散离子纳米粒子只能溶解在有机溶剂中。需要进行复杂的表面改性以使其可溶于水。在本项目中，将探索一种逐步生长的方法来直接合成具有高T1弛豫性能的水溶性ESIONP。ESIONP与生物活性分子的相互作用将作为自我报告的纳米药物递送平台进行研究。该项目将从根本上了解ESIONP与生物活性分子相互作用的T1弛豫率。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。

Nontechnical Summary:This project investigates how magnetic resonance image (MRI) signals change as iron oxide nanoparticles interact with bioactive molecules. The understanding of such signal changes provides a scientific foundation to monitor drug delivery and release using MRI, which will significantly improve the treatment of diseases such as cancer as the dosage and frequency of drugs can be adjusted based on real-time drug uptake information. The major challenges of current approaches for monitoring drug delivery include lack of high sensitivity and limited tissue volume to be imaged. We overcome these challenges by synthesizing high water-soluble iron oxide nanoparticles and using them as MRI agents. MRI is a powerful imaging technique in clinical practice because it provides images with excellent details in a non-invasive, whole-body, and real-time monitoring manner. The multifunctional properties of nanoparticles provide unique advantages for the precise delivery of therapeutic agents with the assistance of imaging. The broad impacts of the project will be achieved by: (1) disseminating the knowledge obtained from this research to the science community for monitoring drug delivery where a non-invasive monitor is extremely important; (2) providing cutting-edge research opportunities for undergraduate and graduate students, particularly those from underrepresented students at Jackson State University (JSU); (3) promoting STEM education via exhibitions during the Mississippi Science Maker at Mississippi Museum of Nature and Science.Technical summary:Nanoparticles can improve drug efficacy and reduce toxicity by altering pharmacokinetics. To track the delivery behavior of drugs, fluorescent tags or radiotracers are usually attached. However, the intrinsic drawback of fluorescent tags lies in the limitation of tissue penetration of light. Availability is a significant challenge for radiotracer approaches. In comparison, iron oxide nanoparticles (IONPs) could be used as a self-reported drug delivery system because of their capability to change water relaxivity in tissue and their excellent biocompatibility. Despite intensive interests, the effect of bioactive molecules on the T1-weighted magnetic property of extrasmall iron oxide nanoparticles (ESIONPs) has not been studied. In addition, the T1 relaxation performance of IONPs is relatively low. The partial reason is that the monodispersal IONPs synthesized by current methods can only be dissolved in an organic solvent. A sophisticated surface modification is required to make them water soluble. In this project, a stepwise growth method will be explored to directly synthesize water soluble ESIONPs with a high T1 relaxation performance. The interaction of ESIONPs with bioactive molecules will be investigated as self-reported nano platform for drug delivery. The project will gain a fundamental understanding of T1 relaxivity of ESIONPs interacting with bioactive molecules.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.