Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

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.

Formulation and candidacidal activity of magnetic nanoparticles coated with cathelicidin LL-37 and ceragenin CSA-13

“…1D) and confirmed by XRD technique (data not shown) 22 . Based on TGA-weight lost and total amount of amine groups on the MNP surface, we calculated that the number of CSA-13 molecules was 3.53 × 10 13 , which corresponds to a number of molecules 20 times lower per 1 µg of compound 22, 23 . However in the case of LL-37, we calculated that the number of cathelicidin molecules was 6.32 × 10 13 , which corresponds to a number of molecules 2.2 times lower per 1 µg of LL-37.

Figure 1Physicochemical features of functionalized magnetic nanoparticles.

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“…In the next step, reaction with glutaraldehyde was performed to obtain a platform for CSA-13 immobilization via imine bonding 22 . In turn, functionalization of aminosilane modified magnetic nanoparticles by cathelicidin LL-37 was achieved by an amidation reaction between the peptide carboxyl group and the primary propyloamine group presented on the MNPs surface 54 .…”

Antibacterial activity of iron oxide, iron nitride, and tobramycin conjugated nanoparticles against Pseudomonas aeruginosa biofilms

“…According to a previous report, iron-oxide in NP form is not only non-toxic, but its byproduct, degraded iron from the cores, apparently accumulates in natural iron stores in the body [113]. Properly biofunctionalized ironoxide NPs have been shown to inhibit growth of Staphylococcus aureus [114][115][116] and Escherichia coli [115,117], prevent biofilm formation by P. aeruginosa [118] and Streptococcus mutans [119], and exhibit bactericidal activity against a range of Gram-negative and Grampositive bacterial species [120][121][122][123][124][125]. While these are very encouraging results, more work is necessary in the investigation of iron-oxide NPs as a feasible alternative to silver NPs in the treatment of bacterial infections and for biofilm disruption.…”

Study on the Antagonistic Potential of Biosynthesized Hematite Nanoparticles During Water and Wastewater Treatment

“…According to Gupta et al, the optical density (OD) of stained biofilm was determined at 595 nm using the plate reader (Tecan Infinite M200, Switzerland). The OD values were considered as an index of biofilm formation by sessile bacteria adhering to the surface . A more intensive antibiofilm effect was considered where a lower absorbance value was detected .…”

“…The OD values were considered as an index of biofilm formation by sessile bacteria adhering to the surface. [35,36] A more intensive antibiofilm effect was considered where a lower absorbance value was detected. [37] The inhibition percentage of biofilm activity was calculated as described in the following equation:…”