Nitric oxide (NO), a free radical endogenously synthesized in the human body, regulates a range of biological processes in the cardiovascular, genitourinary, respiratory, and nervous systems. With the discovery of NO as a potent inhibitor of platelet activation and its identification as an antibacterial agent, the utility of NO has been expanded to developing more biocompatible materials that resist to biofouling. My research has focused on the development of NO-releasing glucose biosensors via xerogel/polyurethane hybrid membranes that release NO in a controlled fashion. This new class of glucose biosensors was characterized by both adequate analytical response to glucose and improved bacterial adhesion resistance at NO fluxes greater than or equal to 5 pmol·cm-2·s-1 for 20 h. To further elucidate the complex and wide ranging roles of NO in physiology, an amperometric xerogel-based NO microsensor was fabricated. Several silicon-based NO sensor membranes were synthesized by doping alkyl/amino-alkoxysilane-based xerogels with Nafion. The performance of xerogel-based NO sensors was then evaluated to identify the optimum xerogel composition that maximized NO permeability and provided sufficient selectivity for NO. Xerogel permeability and selectivity were further manipulated as a function of specific reaction/processing conditions. The analytical performance of the xerogel-based sensor far exceeded that of current commercial sensors. Silica nanoparticles capable of controlled NO release were also synthesized via sol-gel chemistry. Control over both the structure and concentration of the silane precursors (i.e., tetraalkoxy- and aminoalkoxysilanes) and the synthetic conditions used to prepare the silica allowed for the preparation of NO donor-modified silica nanoparticles of widely varying size (d = 20 - 500 nm), NO payloads (50 - 74000 nmol·mg-1), maximum NO release amounts (10 - 103000 ppb·mg-1), half-lives (0.1 - 12 h), and NO release durations (up to 30 h). Nitric oxide-releasing silica nanoparticles may prove useful in the development of glucose sensors with extended NO release durations and as new NO-derived anti-tumor chemotherapeutics. Preliminary studies evaluating the anti-cancer efficacy of NO-releasing silica nanocom-posites against human ovarian surface epithelial (HOSE) cancer cells were conducted. The viability of HOSE cancer cells was significantly reduced upon exposure to the NO-releasing silica nanoparticles. Such scaffolds may allow for future tissue/cell targeting via particle size (enhanced permeability/retention effect) and/or ligand-receptor binding chemistry
