A Self-Circulated Microenvironment-Adaptive Nanozyme for Wound Healing Acceleration

Nanozyme-mediated reactive oxygen species (ROS) homeostasis regulation in vivo is a promising strategy for accelerating the healing of pathogen-infected wounds. It is detrimental in nanozyme preparation to strike a balance between ROS production and scavenging, being adaptive to the wound microenvironment, especially to overcome the irreversible and inevitable inactivation caused by the enzymatic active center loss. Herein, with adjusting ligands and metal charge transfer, we prepared a nanozyme with a regenerated Fe(II) active center, which endowed cyclic and continuous oxidoreductase reactions of peroxidase, superoxide dismutase, catalase, and oxidase under the same neutral pH environment. The versatile enzymatic activity could be easily triggered with oxygen/ROS and cascaded into controllable and reversible ROS generation and scavenging, as well as oxygen release for acceleration of sterilization during infected wound recovery. Under ultralow dosage of Fe-DHB, remarkable effectiveness against 1.0 × 10⁶ drug-resistant bacteria and a wound-healing rate of around 6.3 mm² per day were realized. Our work presents a key breakthrough in nanozyme-based wound healing strategy design.