Pt nanoparticles grown on Bi₃O₄Br nanosheets enhance the efficacy of ampicillin against infectious biofilms

Due to the high resistance and complexity of biofilms, alternatives to traditional antibiotic treatments are urgently needed. Here, we investigated whether Pt nanoparticles grown on Bi 3 O 4 Br nanosheets (Pt NP /Bi 3 O 4 Br) can enhance the efficacy of the antibiotic ampicillin against biofilm-associated infections. X-ray photoelectron spectroscopy revealed abundant oxygen vacancies in the Bi 3 O 4 Br nanosheet creating an ideal surface for Pt nanoparticles growth. The obtained Pt NP /Bi 3 O 4 Br nanozyme had a uniform Pt nanoparticle distribution confirmed by X-ray powder diffraction and transmission electron microscopy with high-angle annular dark-field scanning. Compared to Bi 3 O 4 Br nanosheets alone, the nanozyme demonstrated significantly higher catalytic activity for reactive oxygen species generation facilitated by efficient electron transfer from Pt nanoparticles. When combined with ampicillin, Pt NP /Bi 3 O 4 Br nanozyme significantly enhanced bactericidal efficacy against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli biofilms in vitro as shown by reduction in biofilm thickness and colony-forming units. In a murine skin infection model, the combination accelerated wound healing following S. aureus infection. Additionally, the combined treatment selectively reduced the pathogen Streptococcus mutans in human ex vivo oral biofilms while preserving the healthy human microbiome indicating potential applications in dental care. In conclusion, this work demonstrates that nanozyme-enhanced antibiotic therapy offers a promising strategy to combat biofilm-associated infections and antibiotic resistance. Pt nanoparticles are grown on the Bi 3 O 4 Br nanosheets via a reduction method. The Pt NP /Bi 3 O 4 Br nanozyme generates ROS that degrade extracellular polymeric substances (EPS) in biofilms, therewith enhancing the penetration of ampicillin into biofilms and increase killing of bacteria. • Pt nanoparticles were successfully grown on Bi 3 O 4 Br nanosheets • Pt NP /Bi 3 O 4 Br nanozyme demonstrated high catalytic activity in generating ROS • Pt NP /Bi 3 O 4 Br nanozyme enhanced the antimicrobial activity of ampicillin • Pt NP /Bi 3 O 4 Br nanozyme combined with ampicillin accelerated wound healing in animals • Pt NP /Bi 3 O 4 Br nanozyme and ampicillin reduced pathogenic S. mutans in oral biofilms