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

Abstract

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@PDAFe -CNO NPs. In response to low pH in BME, the decomposition of CaO2 cores generates O2 from one side of Janus NPs to propel biofilm penetration, and the released H2 O2 and Fe2+ produce •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 •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.