Synergistic Antibacterial Activity of Fe <sub>3</sub> O <sub>4</sub> @mPEG-Ag Nanoparticles with Molecular Docking Analyses
Basit Ali Shah, Hongguo Zhu, Asma Sardar, Yuan Gu, Syed Taj Ud Din, Kashif Naseem, Xin‐Yan Wu, Bin Yuan, Bin Yang
Abstract
Objective: This study aims to develop methoxy poly(ethylene glycol) (mPEG) and silver-modified magnetite nanoparticles termed Fe 3 O 4 @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. Fe 3 O 4 @mPEG-Ag NPs were developed as synthetic bactericides that integrate the antibacterial properties of Ag with an excellent stability and dispersibility of mPEG-modified Fe 3 O 4 . Methods: Fe 3 O 4 @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: Fe 3 O 4 @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: Fe 3 O 4 @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.