Self-Propelling Nanomotors Integrated with Biofilm Microenvironment-Activated NO Release to Accelerate Healing of Bacteria-Infected Diabetic Wounds

Diabetic foot ulcer (DFU) treatment is challenged by persistent bacterial infection and hyperglycemia-caused vascular dysplasia. Herein, self-propelled nanomotors are designed to achieve biofilm microenvironment (BME)-activated multistage release of NO for effective sterilization and subsequent angiogenesis promotion. CaO2 nanoparticles (NPs) are capped with PDA layers, followed by complexation with Fe2+ and surface grafting of cysteine-NO to obtain Janus Ca@PDA(Fe)-CNO NPs. In response to low pH in BME, the decomposition of CaO2 cores generates O-2 from one side of Janus NPs to propel biofilm penetration, and the released H2O2 and Fe2+ produce center dot OH through Fenton reaction. The concurrent glutathione-triggered release of NO can be converted into reactive nitrogen species, which exhibit significantly higher bactericidal efficacy than those with only generation of center dot OH or NO. The slow release of NO for an extended time period promotes endothelial cell proliferation and migration. On Staphylococcus aureus-infected skin wounds of diabetic mice, NP treatment eliminates bacterial infections and significantly elevates blood vessel densities, leading to full wound recovery and regeneration of arranged collagen fibers and skin accessories. Thus, the self-propelling and multistage release of NO provide a feasible strategy to combat biofilm infection without using any antibiotics and accelerate angiogenesis and wound healing for DFU treatment.

Automated summary

This study developed self-propelled nanomotors for the treatment of diabetic foot ulcers. The nanomotors released nitric oxide in the biofilm microenvironment to effectively kill bacteria and stimulate angiogenesis. Experimental results demonstrated that the treatment with nanomotors successfully eliminated bacterial infections and promoted wound healing.