A H₂S-Evolving Alternately-Catalytic Enzyme Bio-Heterojunction with Antibacterial and Macrophage-Reprogramming Activity for All-Stage Infectious Wound Regeneration.

Abstract

The disorder of the macrophage phenotype and the hostile by-product of lactate evoked by pathogenic infection in hypoxic deep wound inevitably lead to the stagnant skin regeneration. In this study, hydrogen sulfide (H₂S)-evolving alternately catalytic bio-heterojunction enzyme (AC-BioHJzyme) consisting of CuFe₂S₃ and lactate oxidase (LOD) named as CuFe₂S₃@LOD is developed. AC-BioHJzyme exhibits circular enzyme-mimetic antibacterial (EMA) activity and macrophage re-rousing capability, which can be activated by near-infrared-II (NIR-II) light. In this system, LOD exhausts lactate derived from bacterial anaerobic respiration and generated hydrogen peroxide (H₂O₂), which provides an abundant stock for the peroxidase-mimetic activity to convert the produced H₂O₂ into germicidal •OH. The GPx-mimetic activity endows AC-BioHJzyme with a glutathione consumption property to block the antioxidant systems in bacterial metabolism, while the O₂ provided by the CAT-mimetic activity can generate ¹O₂ under the NIR-II irradiation. Synchronously, the H₂S gas liberated from CuFe₂S₃@LOD under the infectious micromilieu allows the reduction of Fe(III)/Cu(II) to Fe(II)/Cu(І), resulting in sustained circular EMA activity. In vitro and in vivo assays indicate that the CuFe₂S₃@LOD AC-BioHJzyme significantly facilitates the infectious cutaneous regeneration by killing bacteria, facilitating epithelialization/collagen deposition, promoting angiogenesis, and reprogramming macrophages. This study provides a countermeasure for deep infectious wound healing via circular enzyme-mimetic antibiosis and macrophage re-rousing.