Two-Dimensional Metal–Organic Framework/Enzyme Hybrid Nanocatalyst as a Benign and Self-Activated Cascade Reagent for in Vivo Wound Healing

Metal-organic frameworks (MOFs)-based peroxidase mimics have been seldom applied in the biomedical field, especially in vivo. One of the main reasons is their optimum reactions occur in strong acidic environments with a pH of 3-4, severely limiting their applications in living systems where neutral pH is usually required. Other types of peroxidase mimics also suffer such a fatal defect. Additionally, the direct introduction of the relatively high concentrated and toxic reaction reagent H₂O₂ would induce undesired damage to normal tissues. Herein, a MOF-based hybrid nanocatalyst as a benign and self-activated cascade reagent has been constructed. Owing to better catalytic performance compared with three-dimensional bulk MOF, an ultrathin two-dimensional (2D) MOF (2D Cu-TCPP(Fe)) nanosheet is chosen as a model of peroxidase mimic to physically adsorb glucose oxidase (GOx) for fabricating such a hybrid nanocatalyst. Nontoxic glucose can be continuously converted into abundant gluconic acid and H₂O₂ by GOx, avoiding the direct use of relatively high concentrated and toxic H₂O₂ and minimizing the harmful side effects. The generated gluconic acid can decrease the pH value from 7 to 3-4, dramatically activating the peroxidase-like activity of 2D Cu-TCPP(Fe) nanosheets. Meanwhile, the produced H₂O₂ is used for subsequent catalysis of activated 2D Cu-TCPP(Fe) nanosheets, leading to efficient generation of an extremely toxic hydroxyl radial and antibacterial capacity. In vitro and in vivo results illustrate the designed benign and self-activated cascade reagent possesses a robust antibacterial effect with negligible biotoxicity.