The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.Keywords nitric oxide; silica nanoparticle; antibacterial; bactericidal; cytotoxicity; reactive nitrogen species; reactive oxygen species Antibiotic resistance has resulted in bacterial infections becoming the most common cause of infectious disease-related death. 1,2 In the United States alone, nearly 2 million people per year acquire infections during a hospital stay, of which approximately 90,000 die. 2 The primary culprits behind such deadly infections are antibiotic-resistant pathogens, which are responsible for approximately 70% of all lethal nosocomial infections. The growing danger of life-threatening infections and the rising economic burden of resistant bacteria have created a demand for new antibacterial therapeutics.The use of nanoparticles as delivery vehicles for bactericidal agents represents a new paradigm in the design of antibacterial therapeutics. To date, most antibacterial nanoparticles have been engineered using traditional antibiotics that are either incorporated within the particle scaffold or attached to the exterior of the particle. In many cases, such particles have exhibited greater efficacy than their constituent antibiotics alone. For example, Gu et al. reported that vancomycin-capped gold nanoparticles exhibited a 64-fold improvement in efficacy over vancomycin alone. 3 Similarly, silver nanoparticles have schoenfisch@unc.edu. Supporting Information Available: Synthesis of FITC-modified silica nanoparticles, AFM analysis of nanoparticle dimensions, scavenging of NO by TSB, and confocal fluorescence microscopy images of PROLI/NO-treated P. aeruginosa cells. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2013 February 13. shown greater antibacterial activity than silver ion (Ag + ) in solution due to the direct toxicity of the particles and tunable release of Ag + based on nanocomposite size. [4][...

The ability of nitric oxide (NO)-releasing silica nanoparticles to kill biofilm-based microbial cells is reported. Biofilms of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were formed in vitro and exposed to NOreleasing silica nanoparticles. Replicative viability experiments revealed that ≥ 99% of cells from each type of biofilm were killed via NO release, with the greatest efficacy (≥ 99.999% killing) against gram-negative P. aeruginosa and E. coli biofilms. Cytotoxicity testing demonstrated that the highest dose of NO-releasing silica nanoparticles inhibited fibroblast proliferation to a lesser extent than clinical concentrations of currently-administered antiseptics (e.g., chlorhexidine) with proven wound-healing benefits. This study demonstrates the promise of employing nanoparticles for delivering an antimicrobial agent to microbial biofilms.

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A superhydrophobic xerogel coating synthesized from a mixture of nanostructured fluorinated silica colloids, fluoroalkoxysilane, and a backbone silane is reported. The resulting fluorinated surface was characterized using contact angle goniometry, SEM, and AFM. Quantitative bacterial adhesion studies performed using a parallel plate flow cell demonstrated that the adhesion of Staphylococcus aureus and Pseudomonas aeruginosa were reduced by 2.08 ± 0.25 and 1.76 ± 0.12 log over controls, respectively. This simple superhydrophobic coating synthesis may be applied to any surface regardless of geometry and does not require harsh synthesis or processing conditions, making it an ideal candidate as a biopassivation strategy.

Summary The important biological roles of nitric oxide (NO) have prompted the development of analytical techniques capable of sensitive and selective detection of NO. Electrochemical sensing, more than any other NO-detection method, embodies the parameters necessary for quantifying NO in challenging physiological environments such as blood and the brain. Herein, we provide a broad overview of the field of electrochemical NO sensors, including design, fabrication, and analytical performance characteristics. Both electrochemical sensors and biological applications are detailed.