Ceragenin Mediated Selectivity of Antimicrobial Silver Nanoparticles

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• 作者：Mark A. Hoppens ; Christopher B. Sylvester ; Ammar T. Qureshi ; Thomas Scherr ; Desiree R. Czapski ; Randolph S. Duran ; Paul B. Savage ; Daniel Hayes
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2014
• 出版时间：August 27, 2014
• 年：2014
• 卷：6
• 期：16
• 页码：13900-13908
• 全文大小：424K
• ISSN：1944-8252

文摘

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鈥揺lectrospray time-of-flight mass spectrometry (HPLC鈥揈SI-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 卤 38.8 and 102.23 卤 2.3 nm, respectively. The zeta potential of the SNP before and after CSA attachment is 鈭?8.23 and 鈭?.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 渭m 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.

Keywords:

selective antimicrobial; conjugate nanoparticle; specific binding; ceragenin