Degree

Doctor of Philosophy (PhD)

Department

Chemistry and Biochemistry

Document Type

Dissertation

Abstract

Second harmonic generation (SHG) is used to study different types of colloidal nanoparticle drug-delivery systems. The surface charge density, electrostatic surface potentials, and ion adsorptions of 50 nm colloidal gold nanoparticle samples coated with mercaptosuccinic acid are determined using SHG measurements under varying NaCl and MgCl2 concentrations in water. Numerical solutions to the spherical Poisson-Boltzmann equation are fit to the SHG results to account for the nanoparticle surface curvature and ion adsorption to the Stern layer interface, showing excellent agreement with electrophoretic mobility measurements. In another study, nanoparticles of gold, silver and polystyrene are functionalized with microRNA using a nitrobenzyl photocleavable linker that cleaves upon ultraviolet irradiation. The SHG is shown to be a sensitive probe for monitoring the photocleaving dynamics of the oligonucleotides in real time. The photoactivated controlled release is observed to be most efficient on resonance at 365 nm irradiation, with pseudo-first-order rate constants that are linearly proportional to irradiation powers. Silver nanoparticles show an approximate 6-fold plasmon enhancement in photocleaving efficiency over corresponding polystyrene nanoparticles and an approximate 3-fold plasmon enhancement over gold nanoparticles. Additionally, gold-silver-gold core-shell-shell nanoparticles are prepared and are functionalized with miRNA using Diels-Alder chemistry. The plasmonic extinction peak of these nanoparticles, centered at near-infrared (NIR) wavelengths, that can be controlled by varying the thickness of gold and silver shells. Photothermal release of oligonucleotides from the nanoparticle surface under NIR irradiation is studied for drug-delivery applications in the NIR optical window of biological tissue. Lastly, SHG is used to investigate molecular adsorption and transport kinetics of positively charged dyes at the surface of liposomes in water. The adsorption and time-dependent SHG results are analyzed to obtain the free energies of adsorption, the adsorption site densities, and the transport kinetics under varying liposome chemistries and buffer conditions. Parameters such as electrostatic interactions, the chemical structure of the lipid head group, the buffer conductivity, ion-pair formation and adsorbate-adsorbate repulsion are found to influence the adsorption and transport at the liposome surface. In all of these studies, real-time SHG measurements are shown to be highly sensitive for investigating surface dynamics in nanoparticle-based drug delivery systems.

Date

8-4-2017

Committee Chair

Haber, Louis H

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