Synergistic Antibacterial Activity of Fe₃O₄@mPEG-Ag Nanoparticles with Molecular Docking Analyses

Objective: This study aims to develop methoxy poly(ethylene glycol) (mPEG) and silver-modified magnetite nanoparticles termed Fe₃O₄@mPEG-Ag NPs as efficient non-antibiotic antibacterial agents to address the growing challenge of drug-resistant bacterial infections. Impact Statement: This work demonstrates a synergistic nanomaterial design that achieves high antibacterial efficacy, stability, and biocompatibility, positioning it as a promising alternative to conventional antibiotics in combating antimicrobial resistance. Introduction: Infectious diseases caused by drug-tolerant bacteria present a serious global health risk. Fe₃O₄@mPEG-Ag NPs were developed as synthetic bactericides that integrate the antibacterial properties of Ag with an excellent stability and dispersibility of mPEG-modified Fe₃O₄. Methods: Fe₃O₄@mPEG-Ag NPs were fabricated via a serial coprecipitation technique. A series of structural and functional characterizations was performed, and antibacterial activity was tested. Additional assessments included minimum inhibitory concentration (MIC) determination, detailed mechanistic evaluation, cytocompatibility assays, and in silico molecular docking studies. Results: Fe₃O₄@mPEG-Ag NPs demonstrate superior antibacterial activity at a MIC as low as 50 μg·ml^-1 and achieved an efficacy similar to ciprofloxacin. The improved bactericidal effect is attributed to strong electrostatic interactions, membrane disruption through enhanced reactive oxygen species generation under visible light, and intracellular damage via NP penetration and controlled Ag⁺ leaching. Surface functionalization improves colloidal stability and bioactivity while simultaneously maintaining >80% cell viability. Molecular docking further supports the experimental findings by confirming the inhibition of Staphylococcus aureus DNA gyrase and Escherichia coli β-lactamase enzymes. Conclusion: Fe₃O₄@mPEG-Ag NPs demonstrate synergistic antibacterial mechanisms with high biocompatibility, highlighting their potential as effective nanotherapeutics for bacterial control, and represent a promising alternative to conventional antibiotics to combat antimicrobial resistance.