Sprayable self-assembled curcumin-metal-polyphenol nanomedicine with anti-inflammatory, ROS-scavenging and pro-angiogenesis effects for promoting diabetic wound healing

Diabetes wounds present a complex microenvironment characterized by persistent inflammation, elevated reactive oxygen species (ROS), and compromised vascular conditions, all of which contribute to delayed or incomplete healing. Although advances in wound care have been made, effective strategies to address these multifaceted challenges remain limited. In this study, we proposed a self-assembled meta-polyphenol nanoparticle (TA-CU-CCM) loaded with natural products to reshape the local microenvironment and accelerate the healing process in diabetic wounds. The TA-CU-CCM nanoparticles were synthesized through the spontaneous coordination of tannic acid (TA) with copper ions (Cu²⁺), followed by the incorporation of curcumin (CCM), which enhanced the aqueous dispersibility and stability of CCM. Our results demonstrated that this nanosystem significantly improved the biocompatibility and stability of CCM, ensured its sustainable release, and effectively inhibited the inflammatory response via the NF-κB signaling pathway. Additionally, the nanoparticles exhibited notable antioxidant properties, efficiently scavenging ROS to alleviate oxidative stress in fibroblasts, while promoting endothelial cell migration and angiogenesis. <em>In vivo </em>studies further confirmed that the sprayable TA-CU-CCM remodeled the wound microenvironment by facilitating the transition from the pro-inflammatory M1 phenotype to the regenerative M2 phenotype, increasing superoxide dismutase (SOD) activity, and enhancing blood vessel density to promote wound healing in streptozotocin-induced diabetic mice. In conclusion, our findings demonstrate that this multifunctional drug-loaded metal polyphenol nanomedicine holds significant potential for enhancing diabetic wound healing.