title: Ceragenin mediated selectivity of antimicrobial silver nanoparticles.
abstract: The understanding that common broad-spectrum antimicrobials disrupt natural microbial flora important in acquiring nutrients and preventing infection has resulted in a paradigm shift favoring more selective antimicrobials. This work explores silver nanoparticles conjugated with ceragenin, or cationic antimicrobials (CSA-SNPs), as a potential Gram-positive selective antimicrobial. Herein, CSA-SNPs are characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, and high-performance liquid chromatography-electrospray time-of-flight mass spectrometry (HPLC-ESI-TOF-MS). The antimicrobial properties are determined through minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) and time-kill studies. Spatial selectivity of the conjugate nanoparticle was evaluated using confocal imaging, MATLAB statistical analysis, and video monitored interactions between bacteria and CSA-SNPs via laser trapping techniques. Cytotoxicity was also determined by live/dead staining and flow cytometry. Average particle size, as determined through TEM analysis, and hydrodynamic diameter, as determined via DLS, are 63.5 ± 38.8 and 102.23 ± 2.3 nm, respectively. The zeta potential of the SNP before and after CSA attachment is -18.23 and -8.34 mV, respectively. MIC/MBC data suggest that CSA-SNPs are 8 times more effective against Staphylococcus aureus than SNPs alone. Furthermore, MATLAB analysis of confocal imaging found that 70% of CSA-SNPs are within 2 μm of S. aureus, whereas this percentage falls to below 40% with respect to Escherichia coli. These results are bolstered further by laser trapping experiments demonstrating selective adherence of CSA-SNPs conjugates with bacterial strains. Cytotoxicity studies of CSA-SNPs against 3T3 fibroblasts indicate 50% cell viability at 50 ppm.
authors: Department of Biological and Agricultural Engineering, Louisiana State University and LSU Agcenter , 149 E. B. Doran Building, Baton Rouge, Louisiana 70803, United States.
authors: Mark A
authors: MA
authors: Hoppens
authors: Christopher B
authors: CB
authors: Sylvester
authors: Ammar T
authors: AT
authors: Qureshi
authors: Thomas
authors: T
authors: Scherr
authors: Desiree R
authors: DR
authors: Czapski
authors: Randolph S
authors: RS
authors: Duran
authors: Paul B
authors: PB
authors: Savage
authors: Daniel
authors: D
authors: Hayes
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D012834:Silver / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013256:Steroids / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D013256:Steroids; D012834:Silver