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

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 H 2 O 2 , which trigger the decomposition of MnCO into immunomodulatory carbon monoxide (CO) and catalytically active Mn 2+ / 3+ ions. The released Mn 2+ / 3+ ions catalyze H 2 O 2 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.