Dual natural enzyme-tuned biomineralized nanoflowers for boosting cascade catalytic antibacterial therapy and relieving inflammation

The development of the non-antibiotic agents that are clinically safe remains a huge challenge in combating bacterial infections. Herein, we report the construction of dual natural enzymes bromelain (Bro) and glucose oxidase (Gox)-based peroxidase-like nanoflowers through copper phosphate biomineralization for synergistic antibacterial/anti-inflammatory therapy. The hybrid nanoflowers firstly exert the Gox activity for catalyzing the oxidation of glucose to produce H₂O₂, which is subsequently converted into highly reactive ·OH through their peroxidase-like activity. This cascade enzymatic activity endows nanoflowers with excellent antibacterial efficiencies, inhibiting the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by 99% without the addition of exogenous H₂O₂, thus greatly reducing toxic side effects. Meanwhile, the nanoflowers downregulate the secretion of pro-inflammatory cytokines and inhibit the inflammatory response through the release of Bro, significantly accelerating the healing of bacteria-infected wounds. Besides, the nanoflowers utilize the biomolecules and endogenous metal species as building blocks, together with a green and simple synthesis method, guaranteeing their biosafety in practical applications. Overall, the unparalleled biocompatibility and robust antibacterial/anti-inflammatory ability make the nanoflowers a highly promising candidate for the treatment of bacterial infections in future clinical applications.