Development of Multifunctional Gold Nanoparticle Reagents and Applied Use as Metal Ion Sensors, Drug Platforms, and Bioprobes
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Gold nanoparticles are a class of materials expected to have a large impact in future biomedical and environmental applications due to their size-dependent core properties and ease of functionalization. Surface coatings, composed of one or multiple functional ligands, dictate physical properties of the materials and facilitate interactions with molecular species, biomolecules, surfaces, and other nanomaterials. Determining the role of ligand shell composition on nanoparticle reactivity is currently hindered by inadequate synthetic methods to produce well-defined materials. New synthetic approaches are provided in this dissertation to systematically control the number, type, lengths, and steric interactions of functionalized ligands amidst otherwise passivating ligands on gold nanoparticles. Access to these libraries of nanoparticles was afforded by improvements in precursor ligand design, use of a flow reactor for greater reproducibility and high throughput, and corroborative characterization of both the core and ligand shell. Fundamental exploration of nanoparticle structure-reactivity relationships was enabled as a result of synthetic improvements to yield precision controlled multifunctional nanoparticles. The role of polyvalency of malonamide functionalized gold nanoparticles on binding lanthanide ions and nanoparticle assembly is outlined. Findings indicating that low-reactive group densities were most favorable for reactivity and were expanded to produce a more general nanoparticle reagent. Water-soluble gold nanoparticles with a tailored number of azide functional ligands are reported. This azide-nanoparticle building block, or reagent, can be produced in one step, in contrast to typical methods involving inefficient multi-step exchanges. Our reagent was used as a precursor to more complex nanomaterials by “click” chemistry. Finally, gold nanoparticles were produced with drugs modified for surface functionalization. The nanoparticle conjugates with an optimized polyvalency of surface-bound drugs allowed for the binding of a cardiovascular health biomarker enzyme with very high potency. The dissertation work culminated in the production of a fluorescent, drug-loaded, biocompatible probe to visualize targeting on a cellular level. This dissertation includes previously published and unpublished co-authored material.