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Magnetic Resonance as a Useful In Vitro and In Vivo Analytical Tool

Abstract

Magnetic resonance, which exploits the change or difference in magnetic properties of water protons, is a great tool to probe chemical changes. In this dissertation, the application of magnetic resonance as both an in vivo and in vitro analytical tool is explored. Various research groups have studied macromolecular imaging agents. However, only a few hydrogel nanoparticle (nanogels) imaging systems are reported despite their advantages over other systems. These advantages include biocompatibility, high colloidal stability and high water content. In the introduction, a detailed review of applications of nanogels as imaging systems will be provided. It is then followed with the first two chapters of the dissertation, which discuss two innovative MRI imaging nanogel contrast agents we developed. Three novel gadolinium chelate crosslinkers were designed, synthesized, and utilized in the formation of nanogels contrast agents. As a proof of concept, polyacrylamide nanogels chelated with gadolinium were formulated and characterized as MRI contrast agents in chapter 1. To attain better biocompatibility, in chapter 2, polysaccharide-based MRI nanogels were formulated and examined as tumor imaging agents. These MRI nanogels had high colloidal stability, metal chelating stability, and relaxivity, which are essential criteria for clinical contrast agents. Through animal studies, it was shown that theses nanogels not only have high tumor uptake and long retention, but also a high biocompatibility, showcasing their potential to be used in a clinical setting. In addition to in vivo imaging, magnetic resonance is also useful for in vitro analysis. In chapter 3, a novel method utilizing magnetic resonance to monitor and compare release kinetics of payloads from a series of acid-sensitive polymeric nanoparticles is described. While traditional methods of monitoring release kinetics are labor-intensive and unable to probe fast releasing systems, this method is robust, easy, and requires minimal sample amounts. More importantly, it resolves the release kinetics of our series of nanoparticles that could not be accomplished with a traditional Nile red release study

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