Responsive, multimodal imaging agents for MRI: advancing the detection of metals and oxidized species implicated in neurodegenerative disorders

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Responsive, multimodal imaging agents for MRI: advancing the detection of metals and oxidized species implicated in neurodegenerative disorders

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2012-08

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The successful development of responsive, multimodal imaging agents required a bottom-up approach starting with the nature of the iron oxide nanoparticles. Thee relaxivity of the nanoparticles was found to be dependent on the total anisotropy of the particles themselves, which is in turn a function of the size, shape, composition, surface coating, and interparticle distance of the nanoparticles. Responsive, monomodal imaging agents designed to respond to Cu(I) via click chemistry were found to produces significant changes in transverse relaxivity, corresponding to regime changes upon nanoparticle aggregation. These changes agreed well with theoretical modeling and laid the foundation for the subsequent design of multimodal imaging agents.The first multimodal imaging probe, MION@polymer@Ln was designed to maximize relaxivity using a MION@PEG based system. The probe was found to have high relaxivities and exhibited traditional time delayed lanthanide luminescence. The second probe, a core-shell MION@organic@Au multimodal imaging probe was also designed. It was found that the organic intermediate layer maintain the relaxivity of the core nanoparticles, while the gold shell exhibited significant plasmonic absorbance, enabling the probes to function as multimodal imaging probes.Finally, responsive multimodal imaging probes using the previously designed multimodal imaging probes as templates were designed. By using Cu(I) induced aggregation of AuNP and MIONs, the aggregation of the probes was monitored via attenuation of the SPR absorbance and increases in relaxivity. Additional probes using MION@PEG based designs allowed for small molecule (dsDNA) detection as monitored by luminescence quenching and changes in relaxivity.

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University of Minnesota Ph.D. dissertation. August 2012. Major: Chemistry. Advisor: Dr. Valerie Pierre. 1 computer file (PDF); xviii, 193 pages.

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Smolensky, Eric Dominick. (2012). Responsive, multimodal imaging agents for MRI: advancing the detection of metals and oxidized species implicated in neurodegenerative disorders. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/167618.

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