Self-propelled nanomotor enhances MERTK-associated efferocytosis for promoting diabetic wound healing.

Abstract

Impaired antioxidant enzyme activity and dysregulated glucose metabolism in diabetic wounds drive accumulation of advanced glycation end products and reactive oxygen species (ROS), leading to macrophage efferocytosis dysfunction and delayed healing. Although nanozymes hold targeted therapeutic potential, their passive diffusion-dependent transport may limit their ability to penetrate the bacterial biofilm. To address this delivery challenge and achieve immunomodulation, a nanozyme/laser-driven MoS₂/gold nanomotor (MGNM) with cascade catalysis activity was designed for promoting diabetic wound healing. Density functional theory elucidated the heterogeneous metal hybridization strategy enhanced the catalytic activity of MGNM. The asymmetric Janus structure endowed MGNM self-propelled propulsion. Specifically, the MGNM can utilize the wound "pathological substances" glucose/ROS as fuels to generate O₂ via multi-enzyme mimetic cascade catalysis. Meanwhile, the MGNM achieves on-demand photothermal propulsion by near-infrared laser-induced asymmetric thermal gradients. This dual-modal propulsion endows the MGNM with mechanical force to actively penetrate MRSA biofilm in vitro, with the potential to reach wound tissue. Within the tissue, the MGNM exerts its nanozyme-mediated regulatory functions to decrease glucose and ROS levels, promote macrophage efferocytosis, alleviate local inflammation, modulate inflammatory responses and macrophage phenotype, thus accelerate wound repair. This "mechanical penetration-immune regulation" strategy presents a promising therapeutic paradigm for diabetic wound healing.