This study was designed to assess the efficacy of iron oleate lipid nanoparticles (IO-LNPs) in inducing Fenton reaction as a therapeutic approach for bacterial infections caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), both of which are common pathogens in skin wound infections. IO-LNPs were synthesized using the gradient solvent diffusion method, followed by characterization of their particle size, polydispersity index (PDI), zeta potential, and morphology. In vitro antibacterial assays were conducted to evaluate the inhibitory effects of IO-LNPs on bacterial growth
the impact on bacterial viability was confirmed via live/dead staining assays. Furthermore, the mechanism underlying the antibacterial activity of IO-LNPs was investigated. Lastly, in vivo antibacterial studies were performed in a mouse model infected with S. aureus to evaluate the efficacy of IO-LNPs. The results indicated that the IO-LNPs synthesized via the gradient solvent diffusion method possessed a particle size of 114 ± 2 nm, a PDI of 0.198, and a zeta potential of -12.3 ± 1.73 mV. The IO-LNPs demonstrated a significant reduction in the viability of S. aureus and E. coli, effectively inhibiting the formation of biofilms by these bacteria and disrupting pre-existing biofilms. Crucially, in the skin infection model, IO-LNPs significantly inhibited the growth of S. aureus and accelerated wound healing. By day 13, the wound area in the 90 % minimum inhibitory concentration (MIC90) group had decreased to 6.53 %. Collectively, these findings suggest that IO-LNPs, as a novel antibacterial agent, can effectively inhibit bacterial growth and disrupt biofilms by inducing Fenton reaction, thereby demonstrating considerable potential against antibiotic-resistant bacterial infections. This study establishes a theoretical foundation for the development of new treatment modalities for skin wound infections.