Date of Graduation

7-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor

Jingyi Chen

Committee Member

Dan Davis

Second Committee Member

Roger Koeppe

Third Committee Member

Suresh Thallapuranam

Fourth Committee Member

Ryan Tian

Keywords

Pure sciences; Applied sciences; Gold nanostructures; Nanomedicine; Surface modification; Theranosis

Abstract

Noble metal nanostructures have seen a steady increase in biomedical application over the last several decades; new diagnostic and therapeutic modalities are under intense investigation. Many of these applications are possible because of post-synthetic modifications to the particle surface. These modifications take a variety of forms and can significantly affect the pharmacokinetics of these particles. In this work, various surface modifications were investigated. Particle agglomeration, which occurs when particle surfaces remain in contact, can significantly affect the toxicity and efficacy of a nanomedicine. Darkfield microscopy and single-particle ICP-MS were developed as complementary methods to detect agglomeration in blood, with the long-range goal being to establish regulatory mechanisms for nanomedicine. Two novel constructs were developed for such theranostic applications. A hydrophobic photosensitizer was introduced to the surface of poly(ethylene glycol), and its potential was investigated as a photothermal transducer, a photoacoustic contrast agent, and as a delivery vehicle. Relative to the free drug, the construct was found to increase tumor accumulation of the drug in mice and to make the drug more effective as a photodynamic therapeutic. Further surface modification and laser irradiation were able to impart additional control of the release of the drug from the conjugate. Noncovalent interactions were also applied to load and deliver a hydrophilic antibiotic using polydopamine-coated Au nanostructures as a platform. This construct was conjugated with a targeting agent and was then shown to be effective at killing methicillin-sensitive and –resistant strains of S. aureus. Finally, the effect of the anchoring group on AuCu3 nanorod catalysis was investigated using several model reactions and surface ligands, and it was determined that more strongly bound ligands inhibit the catalytic reactions.

Share

COinS