Manganese Carbonyl-Based Peroxidase-like Nanoenzyme Cascading with Glucose Oxidase, Combined with Porphyrin-COFs-Based Phototherapy and CO-Mediated Immunomodulation for Diabetic Wound Repair

Abstract

Abstract Diabetic wounds remain a global health challenge due to vascular insufficiency, bacterial infection, and persistent inflammation. Herein, we designed and prepared a triple-synergistic nanoenzyme platform with antibacterial, anti-inflammatory, and angiogenesis-promoting effects, which was formed by coloading a porphyrin covalent organic framework (Por-COF) with glucose oxidase (GOx) and manganese carbonyl (MnCO). Under near-infrared irradiation, Por-COFs produce a large number of reactive oxygen species (ROS) and localized hyperthermia. Simultaneously, GOx consumes the glucose in wounds to produce gluconic acid and H2O2, which trigger the decomposition of MnCO into immunomodulatory carbon monoxide (CO) and catalytically active Mn2+/3+ ions. The released Mn2+/3+ ions catalyze H2O2 to produce highly toxic •OH through peroxidase-like activity, enhancing bacterial elimination, while the produced CO improves M1-to-M2 macrophage polarization to resolve inflammation and suppresses heat-shock proteins to enhance PTT efficacy. This prepared nanoplatform (Por-COF@GOx/MnCO) achieved more than 99.99% antibacterial efficiency against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus and accelerated wound healing by promoting angiogenesis, ROS scavenging, and immunomodulation. The designed triple-synergistic nanoplatform—integrating glucose oxidase cascading MnCO-based peroxidase-like activity, phototherapy, and CO immunomodulation—shows great potential as a therapeutic strategy for diabetic wound repair.