Dual-responsive glucose/pH degradable nanozyme hydrogel with cascade catalytic antibacterial performance for infected diabetic wound treatment

Diabetic wound infections often lead to excessive inflammation, resulting in chronic or non-healing wounds. Effectively addressing the unique characteristics of the wound microenvironment for precise and safe treatment remains a significant challenge. In this work, we report the construction of novel, capsule-like natural glucose oxidase (GO_x)-loaded metal-phenolic nanozymes (GO_x-Zn²⁺/Cu²⁺-TA-VO_x, GZ-TA-VO_x), which is anchored to a pH/glucose dual-responsive degradable hydrogel composed of poly(vinyl alcohol) (PVA) and phenylboronic-acid-grafted sodium alginate (SA-PBA) for managing bacterial infections in diabetic wounds. The GZ-TA-VO_x nanozymes exhibit efficient peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities, as well as photothermal antibacterial properties. Additionally, the GO_x in GZ-TA-VO_x consumes glucose, producing hydrogen peroxide (H₂O₂) and gluconic acid, which ameliorates hyperglycemia at the wound site and enhances the catalytic activity of the GZ-TA-VO_x nanozymes. Encapsulation in a PVA/SA-PBA hydrogel provides tissue adhesion, self-healing, and degradable properties, enabling controlled drug release and synergistic effects for enhanced wound healing. In vivo experiments demonstrated that the GZ-TA-VO_x hydrogel effectively alleviated inflammation, promoted angiogenesis and epithelial cell proliferation, and facilitated wound recovery, highlighting its potential for managing diabetic wounds. Overall, this work introduces a new synthesis approach for metal-phenolic nanozymes and presents a promising strategy for treating bacterial-infected diabetic wounds.