Polyphenol-functionalized Fe3O4 nanomaterials for combating multidrug-resistant ESKAPE pathogens

Abstract

Antimicrobial resistance among clinically significant Gram-negative ESKAPE pathogens continues to represent a major therapeutic challenge, underscoring the need for nanomaterial-based anti-infective platforms with robust biological performance. Polyphenol-functionalized magnetic nanoparticles may offer a promising strategy for overcoming multidrug resistance and biofilm-associated infections. Fe 3 O 4 nanoparticles functionalized with gallic acid, curcumin, or quercetin were synthesized by in situ alkaline co-precipitation and characterized using XRD, FTIR, TEM, DLS, zeta potential and TGA. Their antimicrobial, antibiofilm, anti-persister, quorum sensing and efflux pump inhibitory activities were evaluated against multidrug-resistant and extensively drug-resistant clinical isolates of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa . Cytocompatibility was assessed using MTT assays. Physicochemical and interfacial analyses confirmed the formation of polyphenol-coated Fe 3 O 4 nanomaterials, with preserved magnetite crystallinity, nanoscale dimensions, negative surface charge, and stable organic loading. In comparison with the corresponding free polyphenols, the nanoformulations exhibited an increase in antibacterial activity, with Fe 3 O 4 @gallic acid showing the most potent effect and a minimum inhibitory concentration of 16 μg/mL against A. baumannii . At sub-inhibitory concentrations, these materials significantly inhibited biofilm formation and diminished mature-biofilm biomass and metabolic activity by up to 78% and 85%, respectively. Notably, Fe 3 O 4 @gallic acid also decreased persister-cell burden by up to 5.0 log 10 CFU/mL, while gene-expression profiling suggested modulation of quorum-sensing and efflux-associated pathways. These findings highlight the potential of polyphenol-functionalized Fe 3 O 4 nanomaterials as promising candidates for localized antimicrobial interventions and antibiofilm surface engineering.