Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles against Nosocomial Pathogens

The effect of nitric oxide (NO)-release kinetics on the antibacterial activity of NO-releasing silica nanoparticles against the nosocomial pathogens Pseudomonas aeruginosa and Staphylococcus aureus is demonstrated. Silica nanoparticles were synthesized and modified to release NO via secondary amine modification with N-diazeniumdiolate NO donors. Planktonic Pseudomonas aeruginosa and Staphylococcus aureus were exposed to a series of NO-releasing silica particles with similar 2 h NO totals but different release kinetics (half-lives). Enhanced antibacterial efficacy was observed against Pseudomonas aeruginosa at pH 7.4 for nanoparticles with faster NO-release kinetics. At pH 7.4, minimal bactericidal efficacy was observed against Staphylococcus aureus, even for silica nanoparticles storing greater NO payloads. However, antibacterial activity was enhanced by exposing Staphylococcus aureus to NO-releasing silica particles at a lower pH (6.4). This was attributed to faster NO-release kinetics at lower pH due to more rapid proton-initiated decomposition of N-diazeniumdiolate NO donors. Collectively, these results demonstrate the enhanced NO-mediated bactericidal efficacy of rapid NO-release kinetics against nosocomial pathogens, providing further insight into the design of NO-releasing materials as novel therapeutics to combat hospital-acquired infections.Bachelor of Scienc