Intelligent Bio-MOF Nanozymes With Dual Antibacterial and Antioxidant Capabilities Through pH-Modulated Double Cascade Reactions for Anti-Fibrosis.

Abstract

Bacterial infection and excessive reactive oxygen species (ROS) in wounds hinder healing and induce fibrosis/scarring. Metal-organic framework (MOF)-based nanozymes integrate MOF's high surface area with nanozyme catalytic properties but face toxicity issues from degradation byproducts. Herein, this study engineered a bio-MOF nanozyme using vitamin B3 as the ligand, featuring stability (the degradation rate was less than 50% in PBS for 28 days), biocompatibility (the bio-MOF nanozyme concentration threshold for cell compatibility was as high as 150 µg/mL), and pH-responsive dual enzymatic activities. In the acidic bacterial microenvironment (pH = 6.5), it activates superoxide dismutase (SOD) and peroxidase (POD) mimetic activities, generating ·OH for bactericidal effects. The antibacterial efficacy against E.coli and S.aureus was both higher than 99%. Under neutral conditions (pH = 7.4), it switches to SOD and catalase (CAT) mimetic modes, scavenging ROS and releasing O₂ to create a reparative microenvironment. In vivo rat infected wound models confirmed enhanced antibacterial efficacy, inhibited excessive fibroblast proliferation, reduced aberrant collagen deposition and scar area, promoting scarless healing. The proposed dual-pathway coordinated regulation of antibacterial-antioxidant mechanisms provides a novel material strategy for addressing cutaneous fibrosis.