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@PDA_Fe -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.

Keywords: Janus nanomotors; biofilm infiltration; diabetic foot ulcers; multistage NO release.