A ruthenium single atom nanozyme-based antibiotic for the treatment of otitis media caused by Staphylococcus aureus

Staphylococcus aureus ( S. aureus ) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C 3 N 4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C 3 N 4 . These metal-C 3 N 4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C 3 N 4 demonstrates the optimal peroxidase-like activity (285.3 U mg –1 ), comparable to that of horseradish peroxidase (267.7 U mg –1 ). In vitro antibacterial assays reveal that Ru-C 3 N 4 significantly inhibits S. aureus growth compared with other metal-C 3 N 4 even at a low concentration (0.06 mg mL –1 ). Notably, Ru-C 3 N 4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C 3 N 4 due to its high peroxidase-like activity. In vivo , Ru-C 3 N 4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C 3 N 4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus -induced OM.