Surface Modification of Noble Metal Nanostructures toward Biomedical Applications

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 longrange 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 polydopaminecoated 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. Acknowledgement I would like to thank my advisor, Professor Jingyi Chen, for her energetic support and guidance. Her patience and open-mindedness allowed me to develop into who I am today. I would like to thank my committee members Profs. Dan Davis, Roger Koeppe, and Suresh Thallapuranam for their helpful suggestions, encouragement, and advice. I offer my sincerest thanks to all of my labmates for their patience and insight. I must thank Dr. Yongbin Zhang for mentoring me during the 2013 summer at the National Center for Toxicological Research, and I must also thank Drs. Paul Howard, Thilak Mudalige, and Taylor Ingle, Ms. Yvonne Jones, and Mr. Bill Monroe for their helpful guidance during the same summer. I appreciate Prof. Min Zou for providing the opportunity and subsequent financial support to develop the nanomaterials lab module. I thank Profs. Tim Muldoon and Julie Stenken for their professional and financial support. I would like to thank Prof. Mark Smeltzer and Mr. Daniel Meeker for the patience, faith, and hard work. I also thank all of my numerous coauthors for their contributions to this text. I would also like to thank Drs. Denise Greathouse, Srinivas Jayanthi, and Geoff Keeler for their expertise and technical advice. Dedication This dissertation is dedicated to my mother for her unwavering support and my father for his inspring memory. Table of