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A ruthenium single atom nanozyme-based antibiotic for the treatment of otitis media caused by Staphylococcus aureus
Jie Wang1, Rui Gong1,2, Ming Yang3
1Nanozyme Synthesis Center, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Insights
A novel nanozyme, Ru-C3N4, effectively combats Staphylococcus aureus infections and otitis media in mice. This single-atom nanozyme shows promise as a targeted antibiotic alternative, degrading biofilms and reducing inflammation without significant toxicity.
Area of Science:
- Materials Science
- Nanotechnology
- Biomedical Engineering
Background:
- Staphylococcus aureus (S. aureus) is a major cause of otitis media (OM), leading to widespread antibiotic use.
- Antimicrobial resistance (AMR) is a growing global health concern due to antibiotic overuse.
- Nanozymes offer a promising alternative to traditional antibiotics for combating AMR.
Purpose of the Study:
- To synthesize and evaluate single-atom nanozymes (SANzymes) for treating S. aureus-induced otitis media.
- To investigate the antibacterial activity and biofilm degradation capabilities of metal-loaded C3N4 SANzymes.
- To assess the in vivo efficacy and safety of the most potent SANzyme in an OM mouse model.
Main Methods:
- Synthesis of metal-C3N4 SANzymes by loading Ag, Fe, Cu, and Ru onto g-C3N4.
- Evaluation of peroxidase-like activity and antibacterial efficacy against S. aureus in vitro.
- Assessment of biofilm degradation and in vivo treatment of OM in mouse models.
- Toxicity assessment in blood, liver, and kidney.
Main Results:
- Ru-C3N4 exhibited optimal peroxidase-like activity, comparable to horseradish peroxidase.
- Ru-C3N4 demonstrated significant in vitro inhibition of S. aureus growth and effective biofilm degradation.
- In vivo studies showed Ru-C3N4 successfully eliminated S. aureus, relieved ear inflammation, and prevented hearing impairment in OM mice.
- The nanozyme showed low toxicity to major organs.
Conclusions:
- Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with high efficacy against Gram-positive bacteria.
- This study presents a novel SANzyme with potential as an effective therapeutic agent for S. aureus-induced otitis media.
- The developed SANzyme offers a safe and effective alternative to traditional antibiotics, addressing the challenge of AMR.
Abstract:
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-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 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-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06 mg mL-1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 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-C3N4 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.
