Co‐Delivery of Morphologically Switchable Au Nanowire and Hemoglobin‐Resveratrol Nanoparticles in the Microneedle for Diabetic Wound Healing Therapy

Diabetic wounds are a common complication of diabetes and pose a significant threat to human health. High glucose concentration in the wound remains a major obstacle, necessitating effective strategies to achieve sustained glucose consumption for synergistic diabetic wound therapy. In this study, an Au-based nanomaterial is developed that can adjust its morphology in different therapeutic processes. The prepared Au nanowire (ANW) can be converted into Au nanospheres (AS) under ultrasonic conditions by adjusting the amount of polyethylene glycol (PEG) on its surface for convenient delivery. Intriguingly, AS is depolymerized into ANW again in the wound area, prolonging the retention time, and ensuring continuous consumption of glucose. After constructing the morphologically switchable Au nanowire, a polyvinyl alcohol (PVA) is applied it to microneedle and co-delivered it with hemoglobin (Hb)-resveratrol (RES) nanoparticles for synergistic diabetic wound therapy. In a streptozotocin (STZ)-induced diabetic mouse model, the microneedle degraded gradually, and the Hb-RES nanoparticles synergistically ameliorated hypoxia, scavenged ROS, and inhibited macrophage differentiation into pro-inflammatory M1 phenotypes. During this process, ANW continuously catalyzed glucose through its inherent glucose oxidase activity. Thus, this study provides novel insights into the long-term management of glucose concentration during synergistic diabetic wound healing.