Pathogen-targeting Bimetallic Nanozymes As Ultrasonic-Augmented Ros Generator Against Multidrug Resistant Bacterial Infection.

Clinical treatment of multidrug resistant (MDR) pathogens-induced infection has emerged as a growing challenge in global public health due to the limited selection of clinically available antibiotics. Nanozymes as artificial enzymes that mimicked natural enzyme-like activities, have received great attention for combating MDR pathogens. However, the relatively deficient catalytic activity in the infectious microenvironment and inability to precisely targeting pathogen restrains their clinical anti-MDR applications. Here, we reported a pathogen-targeting bimetallic BiPt nanozymes for nanocatalytic therapy against MDR pathogen. Benefiting from electronic coordination effect, BiPt nanozymes exhibits dual-enzymatic activities, including peroxidase-mimic and oxidase-mimic activities. Moreover, the catalytic efficiency could be efficiently increased 300-fold by ultrasound under inflammatory microenvironment. Notably, BiPt nanozyme was further cloaked with a platelet-bacteria hybrid membrane (BiPt@HMVs), thus presenting excellent homing effect to infectious sites and precise homologous targeting to pathogen. By integrating accurate targeting with highly efficient catalytic, BiPt@HMVs could eliminate Carbapenem-resistant Enterobacterales (CRE) and Methicillin-resistant Staphylococcus aureus (MRSA) in osteomyelitis rats model, muscle-infected mice model and pneumonia mice model. Our work provides an alternative strategy based on nanozymes for clinically addressing MDR bacteria-induced infections. This article is protected by copyright. All rights reserved.