Development of Chitosan‐Assisted Fe₃O₄@SiO₂ Magnetic Nanostructures Functionalized with Nisin as a Topical Combating System against Vancomycin‐Intermediate Staphylococcus aureus (VISA) Skin Wound Infection in Mice

Abstract

The clinical significance of vancomycin-intermediate S. aureus (VISA) infections is intensified by its tendency to develop resistance to antimicrobials and persistent infections. The decreasing effectiveness of the antimicrobials available is now seriously compromised; thus, there is an emergent need to invent new classes of antimicrobial agents that can rapidly and efficiently eradicate infections. Fe3O4@SiO2@chitosan (CS) nanocomposites were successfully synthesized and then decorated with nisin to gain Fe3O4/SiO2/CS/nisin-based magnetic nanostructures (Fe3O4@SiO2@CS-NISIN). The nanomaterials were characterized comparatively via FTIR (Fourier transform infrared spectroscopy), XRD (X-ray diffraction), FE-SEM (field emission scanning electron microscopes), DLS (dynamic light scattering), and VSM (vibrating sample magnetometer) methods. The methyl thiazol tetrazolium (MTT) assay was performed to determine the inhibitory effects of antibacterial agents on the cell viability. The in vitro bactericidal effect of all compounds was characterized using the microdilution assay. Finally, the topical antibacterial efficacy of free nisin, Fe3O4@SiO2@CS, and Fe3O4@SiO2@CS-NISIN nanocomposites against murine superficial wound infection models was determined. The functionalized nanocomposites were more efficient in suppressing bacterial growth in vitro and in vivo compared to the same quantities of untargeted nanocomposites. MTT results showed acceptable biocompatibility of all nanoformulations, and no substantial difference in the cell viability was recorded between treated cells and untreated control. These results suggest that Fe3O4@SiO2@CS-NISIN nanocomposites can be served as an alternative antimicrobial agent in innovative and emerging technologies to treat a variety of staphylococcal infections.

Adsorption of antimicrobial peptide onto chitosan-coated iron oxide nanoparticles fosters oxidative stress triggering bacterial cell death

“… 44 For Gram-negative bacteria, crowding of metal nanoparticles on the bacterial surface triggers excessive generation of Fe 3+ ions and ROS, leading to cell death. 13 Therefore, cell disruption occurred with time and the highest leakage of cytoplasmic contents was observed at 3.5 hour and also with a higher concentration ratio of nanoconjugate (N-CS-IONP (1 : 4)).…”

“…The results of the study indicated that the addition of chitosan to the magnetic nanoparticles (MNPs) increased the sensitivity of the VISA strain ( S. aureus ), with chitosan-coated MNPs exhibiting up to a 2-fold reduction in both the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) compared to free MNPs. 13 Previous research demonstrated the antimicrobial activity of chitosan, which specifically disrupts the microbial membrane while displaying no toxicity towards mammalian somatic or tumoral cells. 35 In a separate investigation, chitosan polymer exhibited high uptake by mammalian cells and specific binding to the negatively charged bacterial membrane, allowing for the targeted release of tetracycline at the desired site.…”

“…For Gram-positive strains, the antibacterial effects can be stressed upon the release of ROS which arise from the attachment of nanoconjugate to the bacterial cell surface. 13 It can also be hypothesized that attachment of the nanocomposite also releases nisin, which forms pores so the generated Fe 3+ ions are transported inside the cells and interact with biomolecules such as proteins and nucleic acids, impairing enzymatic activity, altering protein structures, and interrupting DNA strands, ultimately leading to cell death. 13 This is evident from the cytoplasmic leakage assay.…”

“… 13 It can also be hypothesized that attachment of the nanocomposite also releases nisin, which forms pores so the generated Fe 3+ ions are transported inside the cells and interact with biomolecules such as proteins and nucleic acids, impairing enzymatic activity, altering protein structures, and interrupting DNA strands, ultimately leading to cell death. 13 This is evident from the cytoplasmic leakage assay. The nanoconjugate showed maximum leakage of cytoplasmic content at 2.5 hour.…”

“…11 For example, studies have shown that iron oxide magnetic nanoparticles loaded with nisin and nystatin have antimicrobial properties against Gram-positive bacteria. 12,13 This suggests that these functionalized nanoparticles have potential applications as antimicrobials in innovative and emerging technologies that utilize magnetic nanomaterials. 12 Antimicrobial peptides (AMPs) have emerged as prospective treatments, exhibiting broad-spectrum efficacy and minimal acquisition of resistance due to their peculiar amphiphilic structure, with polycationic headgroups, enabling them to rupture microbial membranes.…”