Intelligent ROS therapy driven by iron-based nanozyme with controllable catalytic activity for infected wound healing

Therapeutic generation of reactive oxygen species (ROS) through catalytic therapy demonstrates antibacterial efficacy against wound infections. However, prolonged and unregulated ROS production risks inducing intolerable oxidative stress alongside exacerbated inflammatory responses, creating a microenvironment counterproductive to wound healing. Here, inspired by rechargeable batteries, we have developed a catalytic activity-controllable nanozyme by integrating Fe^(II) and Fe^(III) within metal-organic frameworks (FeNZ). Specifically, the overexpressed glutathione in the infective wound can increase the Fe^(II) fraction in FeNZ and endow FeNZ with peroxidase (POD)-like activity, which can convert hydrogen peroxide (H₂O₂) into hydroxyl radicals (•OH) for effective eradication of both drug-sensitive and drug-resistant bacteria (Staphylococcus aureus, 97.9% of antibacterial rate; methicillin-resistant S. aureus (MRSA), 93.2% of antibacterial rate) by disrupting bacterial membranes. Of note, the catalytic performance of FeNZ declined in parallel with the increase in Fe^(III) content during the •OH generation process, resulting in a low inflammatory microenvironment for infected wound healing and faster wound healing (95.5% of healing rate for FeNZ + H₂O₂ group, 83.5% of healing rate for Control group, day 16). The activity-controllable FeNZ thus holds promise as an effective agent for bacterial elimination and enhanced wound repair, presenting a novel strategy for the management of infected wounds.