The proposed research will explore new strategies in nanomedicine and develop novel materials for drug delivery, molecular imaging, proteomics and metabolomics. The four main objectives can be summarized as nanoparticle assembly, application of nanoparticles to molecular imaging, novel ligand design for drug delivery and viral detection and inhibition. Assembly of nanoparticles into unique signalling platforms will be achieved via novel ligand design for gold and silver nanoparticles and will enhance the utility of such particles towards molecular imaging. Success will make vibrational microscopy using functionalized nanoparticles a viable alternative to fluorescent probes for medical imaging.
Applications in molecular imaging will focus on visualizing proteins at the surface of neurons with glycosylated nanoparticles to understand how these signalling proteins change in number and localization in response to stimuli and how these protein traits vary between healthy and diseased neurons. These data are critical in understanding the causes and progression of neurodegenerative diseases. This research will result in novel opportunities for therapeutic intervention, which itself may be possible using the functionalized nanoparticles as drug delivery agents. Glycosylation of the surface of the nanoparticles is critical for improving the bioavailability of nanoparticles for this objective. In the third objective of this project, photo-cleavable groups will be introduced into the nanoparticle ligand framework and used to release drugs at targets upon two-photon excitation of the nanoparticles. Thereby a single photon is emitted that can cleave the photo-labile group binding the drug to the particle.
Finally, glycosylated nanoparticles will be used to image hepatitis C viral particles in vivo and to inhibit their entry into liver cells.
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