Peptide-induced functionalization of superparamagnetic silver-conjugated iron oxide nanocomposites for enhancing antibacterial activity

Abstract

When antimicrobial peptides and nanomaterials are integrated, synergistic antibacterial effects are exhibited. Peptides as ligands have been used to construct ideal antibacterial agents, and herein, peptide-modified silver-conjugated iron oxide nanocomposites were successfully prepared. The formed Fe₃O₄ core with sufficient magnetic properties via co-precipitation was coated with a polydopamine (PDA) intermediate layer to form Fe₃O₄@PDA. Due to the groups binding and reducing silver ions in Fe₃O₄@PDA, an Ag nanoshell with high bacteriostatic activity was deposited on the surface of Fe₃O₄@PDA to form Fe₃O₄@PDA-Ag. The synthetic peptide CA₂R₅ was beneficial for binding with bacterial surfaces through electrostatic interactions, and it was used to modify Fe₃O₄@PDA-Ag to form the Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite. The Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite produced higher antibacterial activity than the Fe₃O₄@PDA-Ag nanocomposite, confirming their synergistic antibacterial effect. The minimum bactericidal concentration (MBC) of the Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite against Staphylococcus aureus or Escherichia coli was 0.6 µg mL⁻¹ Ag. The Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite with the same MBC also killed four additional bacterial species (Listeria monocytogenes, Shigella castellani, Salmonella typhimurium, and Pseudomonas aeruginosa). The bactericidal activity of the Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite against S. aureus remained above 80% after five cycles of antibacterial action and magnetic separation. The antibacterial activity of the Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite was stable across different pH conditions (4, 7.4, and 9) and storage time (within 30 days). In the presence of external H₂O₂, the Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite with high peroxidase (POD)-like activity exhibited a stronger bactericidal performance due to the production of ˙OH. The death of the bacteria was attributed to the disrupted integrity of the bacterial cell. Fe₃O₄@PDA-Ag-CA₂R₅ with 6-fold MBC was not toxic to living organisms. The synthesized Fe₃O₄@PDA-Ag-CA₂R₅ nanocomposite in our work possessed strong bactericidal ability, broad antibacterial spectrum, satisfactory recyclability, high stability, high POD-like activity, and excellent biocompatibility, thus providing a promising strategy for building robust antibacterial agents.