A cascade nanozyme with antimicrobial effects against nontypeable Haemophilus influenzae

Otitis media (OM) is the main cause of pediatric antibiotic prescriptions. Nontypeable Haemophilus influenzae (NTHi) is a major OM pathogen, which forms a biofilm that resists conventional antimicrobials and immune clearance. Thus, novel treatments that are effective against NTHi and its biofilm are urgently required. Nanozymes (often inorganic nanoparticles) mimic natural enzymes' catalytic activities to generate strong antimicrobials at the site of infection, and thus represent one of the emerging solutions to the crisis of antimicrobial resistance. They mimic natural enzymes' activities, such as generating strong antimicrobials catalytically at the site of infection, to minimize overexposure. However, that in situ generation often relies on Reactive Oxygen Species (ROS) as precursors, a prerequisite that limits the broad deployment of nanozymes. To address this challenge, we designed a cascade nanozyme that generates an antiseptic, HOBr, from a ubiquitous non-ROS, i.e., O-2, which successfully eradicates NTHi. The cascade nanozyme simultaneously exhibits glucose oxidase (GOx)-like activity from gold nanoparticles (AuNPs) and haloperoxidase (HPO)-mimicking activity from vanadium pentoxide nanowires (V2O5 NWs) connected using dopamine (DPA). The cascade nanozyme demonstrated strong antimicrobial efficacy against NTHi and its biofilm, while showing improved biocompatibility compared to the nanozyme of V2O5 NWs alone. The cascade nanozyme thus points to a material-oriented infectious disease treatment strategy, where small-molecule antimicrobials are generated in real time at the site of infection for the benefit of autonomous dosing. This strategy potentially mitigates the development of antimicrobial resistance and reduces side effects.