| dc.description.abstract | The field of nanomedicine capitalizes on the unique chemical and physical properties of nanoscale materials. Tuning parameters such as the shape, size, and elemental composition of nanomaterials has allowed scientists to identify important trends needed to optimize biological activity, but surface structural elements have received significantly less attention. The impact of spatial constraint of peptides attached to the surface of gold nanoparticles, for example, has remained relatively unexplored. As protein conformation is well-known to affect biological activity, it was hypothesized that the same would hold true for smaller biomimetic peptides. This was evaluated by conjugating RGD-containing peptide sequences to gold nanoparticles in mono- and bidentate fashions and subsequently evaluating the ability of the nanoconjugates to enhance radiosensitivity in vitro. PEGylated gold nanoparticles bearing mono- and bidentate peptide epitopes of the protective antigen of Bacillus anthracis were also evaluated in a murine model to determine their ability to stimulate a humoral immune response. In both studies, the bidentate “looped” peptides exhibited greater biological activity, suggesting that the spatial constraint of biomimetic peptides on the surface of gold nanoparticles should no longer be ignored. Herein is also described work towards orthogonally functionalizing separate faces of a gold nanoparticle to create a particle with biologically relevant Janus character. Various monolayer protected gold nanoparticles underwent place exchange with ligands of a second type to create mixed monolayers whose nanoscale patterning was driven by entropy and enthalpy, and the extent of phase separation was characterized with MALDI-IM-MS and NOESY. The final portion of this dissertation describes the fabrication and validation of microfluidic devices designed to be interfaced with organ-on-chip platforms. This includes a microformulator capable of performing automated, user-defined chemical perturbations and a microclinical analyzer which electrochemically monitors concentrations of various metabolites using enzymatic biosensors. When combined, these investigations address all four subfields of nanomedicine (preventive, diagnostic, therapeutic, and toxicology) and represent the ongoing efforts to harness the novel properties of nanomaterials to enhance the length and quality of human life. | |
