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

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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.