Neutrophil Extracellular Traps-Inspired Hydrogen-Bonded Organic Framework-Based Bio-orthogonal Nanozymes for Enhanced...

Neutrophil extracellular traps (NETs) represent innate antimicrobial microstructures composed of DNA and various proteins and enzymes. NETs can trap microorganisms and then achieve a sterilization effect through reactive oxygen species (ROS) and cationic antimicrobial peptides. While these web-like structures physically constrain microbial dissemination, the inherent instabilities, including nuclease-mediated DNA degradation and protease-sensitive antibacterial peptides, limit the antibacterial therapeutic effect of natural NETs. To address the above critical limitations, herein, we propose hydrogen-bonded organic framework-based bio-orthogonal nanozymes (HbioNzyme) that synergistically combine peroxidase-mimetic activity with click catalytic functionality to mimic the antibacterial functions of NETs. Importantly, the NETs-like HbioNzyme networks decorated with spiky nanoarchitectures almost completely capture pathogenic bacteria, facilitating in situ ablation of bacteria by the activated ROS and antimicrobial agents. Mechanism studies reveal that the bio-orthogonal nanozymes not only enable activation of antimicrobial components but also enhance membrane penetration through spike-bacterial surface interaction. This bioinspired engineering strategy establishes a paradigm for developing next-generation antimicrobial platforms, which synergize physical capture with the activation of chemicals, paving a way for advanced nanotherapeutics against pathogenic bacterial infections.