Development of organic-inorganic nanoparticle hybrid systems for medical applications

Light has been efficiently used to control molecules and materials. Integration of photo-responsive molecules into larger molecular systems allows for the use of light to regulate the physical and chemical properties of these systems and to control their activity. The way in which a photoresponsive moiety is used depends on its response to the light signal and its interaction with other components in the molecular system. Based on their structure, some chromophores translate light signals into chemical, structural or electronic changes, while others convert the light signal into another type of energy signal (such as heat) that can trigger changes in a molecular system. The work presented in this thesis examines the design, preparation and evaluation of two light-controlled biomedical molecular systems utilizing different types of photo-responsive molecules.In the first study, featured in Chapter 2, light is used to control the activity of a nanoparticle-based MRI contrast agent. The design relies on the photochromic properties of spiropyran ligands to induce photo-control over the ability of the surrounding water molecules to access the surface of NaGdF4 nanoparticles, and consequently affect their proton relaxivity. The optimized structure of the spiropyran ligand was synthesized, and the photoswitching behaviour between the two isomers, with distinct polarities, was evaluated in an aqueous medium for both free and anchored versions. The designed nanoassembly enhanced the relaxivity of water protons, although displayed a small change in activity upon irradiation with visible light, which was attributed to the high magnetic field at which the data was acquired.In the second study, featured in Chapter 3, light is used to activate thermally-responsive enediyne molecules and generate reactive radicals that can potentially be used to destroy cancer cells. The design utilizes the photothermal effect of gold nanoparticles to transform the light energy into localized heat energy. The room temperature stable enediyne ligand was synthesized and then attached to the surface of the gold nanoparticles. Irradiation of the nanoassembly with a nanosecond pulsed green laser for three minutes generated enough heat to trigger the cyclization reaction of the enediyne decorated nanoparticles and release the activated enediyne ligands from gold nanoparticle surface.