Oxygen Vacancy‐Rich Amorphous MOF/Graphene Nanozymes With Self‐Sustaining Catalytic Circuits for Drug‐Resistant Infection Wound Healing

Diabetic chronic wounds, driven by hyperglycemia-induced oxidative stress and multidrug-resistant bacterial infections, represent a highly challenging clinical issue. Existing therapies fall short in addressing the dual challenges of bacterial resistance and dysregulated wound microenvironments. Although metal-organic framework (MOF)-based nanozymes hold potential for catalytic antibacterial therapy, their clinical application is limited by insufficient active site exposure, structural instability of amorphous MOFs (aMOFs), and dependence on toxic exogenous H₂O₂. Here, a triple-engineered cascade nanozyme (aMrGG) is presented that synergizes amorphous Fe-MOF chemistry, graphene interface engineering, and glucose-fueled metabolic reprogramming to overcome these barriers. Through thermal reduction-induced amorphization, aMOFs exhibit a 2.1-fold enhancement in peroxidase-like activity, driven by abundant oxygen vacancies and an optimized Fe²⁺/Fe³⁺ ratio. Mechanochemical anchoring of aMOFs onto reduced graphene oxide (rGO) stabilizes catalytic performance and enhances charge transfer, resulting in a 13.3-fold increase in hydroxyl radical (·OH) generation. The self-sustaining cascade system, powered by endogenous glucose in diabetic wounds, produces nontoxic H₂O₂ and lowers the pH to 3.5, activating nanozyme activity while protonating bacterial membranes for targeted ·OH attack. In vivo, aMrGG achieves >99.999% eradication of MRSA and E. coli, accelerates wound healing. This study pioneers the amorphous materials in microenvironment-adaptive nanomedicinefor diabetic wound management.