AMP-Coated TiO2 Doped ZnO Nanomaterials Enhanced Antimicrobial Activity and Efficacy in Otitis Media Treatment by Elevating Hydroxyl Radical Levels

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health.Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed.Methods: ZnO@TiO 2 @AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization.The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated.For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs.Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%.Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 μg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 μg/mL.In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane.Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs.Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (•OH) compared to ZnO NPs.Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro.This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.