A Comparative Analysis of the Antibacterial Spectrum of Ultrasmall Manganese Ferrite Nanozymes with Varied Surface Modifications

Bacterial infectious diseases pose a significant global challenge. However, conventional antibacterial agents exhibit limited therapeutic effectiveness due to the emergence of drug resistance, necessitating the exploration of novel antibacterial strategies. Nanozymes have emerged as a highly promising alternative to antibiotics, owing to their particular catalytic activities against pathogens. Herein, we synthesized ultrasmall-sized MnFe₂O₄ nanozymes with different charges (MnFe₂O₄-COOH, MnFe₂O₄-PEG, MnFe₂O₄-NH₂) and assessed their antibacterial capabilities. It was found that MnFe₂O₄ nanozymes exhibited both antibacterial and antibiofilm properties attributed to their excellent peroxidase-like activities and small sizes, enabling them to penetrate biofilms and interact with bacteria. Moreover, MnFe₂O₄ nanozymes effectively expedite wound healing within 12 days and facilitate tissue repair and regeneration while concurrently reducing inflammation. MnFe₂O₄-COOH displayed favorable antibacterial activity against Gram-positive bacteria, with 80% bacterial removal efficiency against MRSA by interacting with phosphatidylglycerol (PG) and cardiolipin (CL) of the membrane. By interacting with negatively charged bacteria surfaces, MnFe₂O₄-NH₂ demonstrated the most significant and broad-spectrum antibacterial activity, with 95 and 85% removal efficiency against methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa, respectively. MnFe₂O₄-PEG dissipated membrane potential and reduced ATP levels in MRSA and P. aeruginosa, showing relatively broad-spectrum antibacterial activity. To conclude, MnFe₂O₄ nanozymes offer a promising therapeutic approach for treating wound infections.