Natural agents derived Pickering emulsion enabled by silica nanoparticles with enhanced antibacterial activity against drug-resistant bacteria

• A novel natural antibacterial agents derived Pickering emulsion (FLTPE) has been designed for the first time. • FLTPE shows enhanced antibacterial performance due to synergistic bacterial cell wall and cell membrane dual destruction function. • FLTPE provides superior efficacy in healing drug-resistant bacteria-infected wounds in mice compared to ampicillin. The emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) has become a global health challenge due to the overuse of antibiotics. Natural substances including enzymes and essential oils have shown great potential as alternative treatment options. However, the combinational use of these natural agents remains challenging due to the denaturation of enzymes upon direct contact with oil. In this study, we report the design of a Pickering emulsion containing two natural antibacterial agents, lysozyme and tea tree oil, stabilized by fractal silica nanoparticles. In this design, the enzyme activity is kept and the volatility problem of tea tree oil is mitigated. Due to synergistic bacterial cell wall digestion and membrane disruption functions, potent bactericidal efficacy in vitro against drug-resistant bacteria is achieved. The therapeutic potential is further demonstrated in a wound healing model with drug-resistant bacteria infection, better than a synthetic antibiotic, Ampicillin. This study opens new avenues for the development of natural product-based antimicrobial treatments with promising application potential.