Abstract
BackgroundCeragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity.ResultsOur studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface.ConclusionOur results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.
Highlights
Ceragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents
Our results suggest that immobilization of CSA-13 on the magnetic nanoparticles (MNPs) surface significantly reduces membrane toxicity to red blood cell (RBC) and increases antimicrobial activity against selected bacteria
We anticipate that amine group at the C3 position in CSA-13 is the primary site of reactivity because it is less sterically hindered than other amines in the molecule
Summary
Ceragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity. Ceragenin CSA-13 belongs to family of synthetic mimics of cationic antimicrobial peptides (CAPs) that display strong antibacterial activities [1,2]. Cationic lipids such as CSA-13 are easier to prepare and purify than antimicrobial peptides [3]. Our results suggest that immobilization of CSA-13 on the MNP surface significantly reduces membrane toxicity to RBCs and increases antimicrobial activity against selected bacteria
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