title: Kinetic-dependent Killing of Oral Pathogens with Nitric Oxide.
abstract: Nitric oxide (NO)-releasing silica nanoparticles were synthesized via the co-condensation of tetramethyl orthosilicate with aminosilanes and subsequent conversion of secondary amines to N-diazeniumdiolate NO donors. A series of ~150 nm NO-releasing particles with different NO totals and release kinetics (i.e., half-lives) were achieved by altering both the identity and mol% composition of the aminosilane precursors. Independent of identical 2 h NO-release totals, enhanced antibacterial action was observed against the periodontopathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis with extended NO-release kinetics at pH 7.4. Negligible bactericidal effect was observed against cariogenic Streptococcus mutans at pH 7.4, even when using NO-releasing silica particles with greater NO-release totals. However, antibacterial activity was observed against S. mutans at lower pH (6.4). This result was attributed to more rapid proton-initiated decomposition of the N-diazeniumdiolate NO donors and greater NO-release payloads. The data suggest a differential sensitivity to NO between cariogenic and periodontopathogenic bacteria with implications for the future development of NO-releasing oral care therapeutics.
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Backlund
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: B V
authors.initials: BV
authors.lastname: Worley
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Sergesketter
authors.affiliation: Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA schoenfisch@unc.edu.
authors.forename: M H
authors.initials: MH
authors.lastname: Schoenfisch
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000187:drug effects*; D013295:Streptococcus mutans / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D009569:Nitric Oxide
keywords: Aggregatibacter actinomycetemcomitans; N-diazeniumdiolate; Porphyromonas gingivalis; dental caries; periodontal disease; silica