Nanozymes-Armed Probiotic Lactobacillus plantarum Coordinates Ferroptosis-like Bacterial Death for Diabetic Wound Therapy

High-glucose microenvironment in diabetic wound exacerbates the risk of bacterial infections and perpetuates chronic inflammation, thereby complicating wound healing. To meet these challenges, we develop antibacterial agents by integrating probiotics with nanozymes targeting high glucose levels and multidrug-resistant bacterial infections in diabetic wound healing. We engineer probiotic Lactobacillus plantarum (LP) with Fe-based nanozymes containing glucose oxidase (GOx) as antibacterial agents (LP@FeG) for diabetic wound therapy. The bioactivity of LP ferments glucose in the wounds, thereby reducing local pH through lactic acid production. Besides, GOx catalyzes the conversion of glucose into gluconic acid and hydrogen peroxide, further lowering local pH. In addition, GOx stimulates the peroxidase-like activity of Fe-based nanozymes, thereby generating reactive oxygen species that attack the cellular membrane, facilitating the entry of Fe 2+ /Fe 3+ into bacteria and inducing bacterial death through ferroptosis and lipid peroxidation. In vivo studies demonstrate that LP@FeG exhibits prolonged sterilization of methicillin-resistant Staphylococcus aureus with an almost 100% antibacterial rate, marked anti-inflammatory, and proangiogenic effects in diabetic wounds. This strategy resolves both the high glucose level and bacterial infections in wound healing, being promising for the treatment of diabetic wounds.