Abstract
Although Zeolitic Imidazolate Framework-8 (ZIF-8) shows significant promise in chemodynamic therapy of bacterial infections due to its large specific surface area and enzyme-like activity, it still faces a considerable gap compared to natural enzymes. The dependency on low pH and high concentrations of hydrogen peroxide ((H(2)O(2)) is a major factor limiting the clinical progress of nanozymes. Single-atom nanozymes (SA-zyme), which exhibit superior catalytic performance, are expected to overcome this limitation. In this study, we used ZIF-8 as a template to prepare structurally regular molybdenum-based single-atom nanozymes (Mo-zyme) by coordinating molybdenum atoms with nitrogen atoms within the zeolitic imidazolate framework and evaporating the zinc element at high temperatures. The cascade catalytic performance of the nanodrugs was enhanced by loading glucose oxidase (GOx) and encapsulating it with a hyaluronic acid (HA) layer to form a composite (Mo/GOx@HA). Upon contact with hyaluronidase from bacteria in infected tissues, the cascade reaction is triggered, resulting in the degradation of the HA shell, and releasing the encapsulated GOx. Once exposed, GOx catalyzes the oxidation of glucose into gluconic acid, resulting in a localized decrease in pH and continuous production of H(2)O(2). The combination of lowered pH and increased H(2)O(2) concentration significantly amplifies the catalytic activity of the Mo-zyme. This enhanced activity facilitates the in situ generation of hydroxyl radicals (•OH) on the bacterial surface, leading to effective and efficient bacterial eradication. Wound infection treatment has demonstrated that the as-prepared Mo/GOx@HA exhibits excellent antibacterial and anti-inflammatory activity. This work provided a promising enzymatic cascade reaction nanoplatform for the treatment of bacteria infected wounds.