title: Dual action antimicrobials: nitric oxide release from quaternary ammonium-functionalized silica nanoparticles.
abstract: The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles with and without nitric oxide (NO) release capabilities is described. Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl, butyl, octyl, and dodecyl) were tethered to the surface of amine-containing silica nanoparticles via a ring-opening reaction. Secondary amines throughout the particle were then functionalized with N-diazeniumdiolate NO donors to yield dual functional nanomaterials with surface QAs and total NO payloads of 0.3 μmol/mg. The bactericidal activities of singly (i.e., only NO-releasing or only QA-functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional nanoparticles were tested against Gram-positive  Staphylococcus aureus  and Gram-negative  Pseudomonas aeruginosa . Particles with only NO release capabilities alone were found to be more effective against  P. aeruginosa , while particles with only QA-functionalities exhibited greater toxicity toward  S. aureus . The minimum bactericidal concentrations (MBC) of QA-functionalized particles decreased with increasing alkyl chain length against both microbes tested. Combining NO release and QA-functionalities on the same particle resulted in an increase in bactericidal efficacy against  S. aureus ; however, no change in activity against  P. aeruginosa  was observed compared to NO-releasing particles alone.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Alexis W
authors.initials: AW
authors.lastname: Carpenter
authors.forename: Brittany V
authors.initials: BV
authors.lastname: Worley
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Slomberg
authors.forename: Mark H
authors.initials: MH
authors.lastname: Schoenfisch
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000644:Quaternary Ammonium Compounds; D009569:Nitric Oxide; D012822:Silicon Dioxide