Biocompatible WSe₂ Nanosheet Antibiotics for The Therapy of Pathogenic Bacterial Infections

Abuse of broad-spectrum antibiotics not only causes intestinal microbial imbalance but also emerges bacteria resistant to drugs. Therefore, it is an urgent task to develop narrow-spectrum antibiotics and new bactericidal mechanisms to overcome the limitations of broad-spectrum antibiotics. Herein, we present ultrathin WSe₂ and MoSe₂ nanosheets exfoliated and functionalized with poly(acrylic acid) (PAA-WSe₂ and PAA-MoSe₂) in an aqueous solution as a narrow-spectrum antibiotic or a species-specific agent, respectively, for treatment of bacterial infection diseases. PAA-WSe₂ nanosheets exhibited bactericidal activity only against gram-positive bacteria including multidrug-resistant <i>S. aureus</i>, whereas PAA-MoSe₂ showed selective bactericidal activity against <i>S. aureus</i> only. Moreover, PAA-WSe₂ accelerated the oxidation-reduction reaction mediated by lipoteichoic acid, a component of the cell membrane of gram-positive bacteria, producing Se⁴⁺ for antibacterial activity. Subsequently, the PAA-WSe₂ nanosheets induced depolarization and disruption of the bacteria-cytoplasmic membrane for the complete eradication of gram-positive bacteria. PAA-TMD nanosheets, including PAA-WSe₂ and PAA-MoSe₂, also exhibited outstanding biocompatibility against normal cells and hemocompatibility with red blood cells. Finally, PAA-WSe₂ nanosheets effectively eradicated <i>S. aureus</i> infecting the wounds of mice, showing excellent therapeutic effects <i>in vivo</i>. These results suggest that PAA-WSe₂ has been developed as a narrow-spectrum antibiotic used for various bacterial infections.