Multifunctional nanozyme capsule for sensitive bacterial detection and synergistic antibacterial therapy

Abstract

The escalating global proliferation of antibiotic-resistant pathogens poses unprecedented challenges to public health, demanding innovative platforms that integrate rapid pathogen identification with enhanced antimicrobial efficacy. Here, we engineer a stimuli-responsive nanozyme capsule (Zn/Fe-ZIF-NP) for dual-modal bacterial detection and synergistic antimicrobial action against drug-resistant strains. Zn/Fe-ZIF-NP encapsulates both a fluorochrome (6-Hydroxyfluorescein, FAM) and antibacterial agent ciprofloxacin (CIP) within bimetallic zeolitic imidazolate framework nanoparticles, thereby enabling dual functionalities: visual detection of bacteria and synergistic antibacterial efficacy. The Zn/Fe-ZIF-NP exhibits peroxidase-like activity, converting H₂O₂ into bactericidal hydroxyl radicals (•OH) that induce oxidative stress in bacteria by damaging their membrane lipids. Using Escherichia coli and Staphylococcus aureus as models, Zn/Fe-ZIF-NP undergoes bacteria-activated degradation. Bacterial adenosine triphosphate (ATP) release triggers nanoparticle breakdown, which liberates FAM for fluorescence detection and CIP for antimicrobial action. The combined action of CIP and Zn/Fe-ZIF-NP further promotes ATP leakage, accelerating nanoparticle degradation and enhancing antibacterial activity. When the concentration of CIP@Zn/Fe-ZIF-NP reached the minimum bactericidal concentration (MBC) of 80 μg/mL, the bactericidal efficiency against both bacterial strains approximately 98 %. Moreover, the ZIF structure acts as protective carriers for the encapsulated agents, minimizing CIP loss and maintaining antibiotic activity. This multifunctional nano-capsule system integrates diagnostics and therapy by combining nanozymes, antibiotics, and fluorescent signaling, enabling pathogen detection and combating drug-resistant infections.