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

Abstract 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 H 2 O 2 . 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 Fe 2 ⁺/Fe 3 ⁺ 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 H 2 O 2 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.