Biomimetic hybrid nanovesicles improve infected diabetic wound via enhanced targeted delivery.

Infected diabetic wounds have been raising the global medical burden because of its high occurrence and resulting risk of amputation. Impaired endothelium has been well-documented as one of the most critical reasons for unhealed wounds. Recently, endothelial cell-derived nanovesicles (NVs) were reported to facilitate angiogenesis, whereas their efficacy is limited in infected diabetic wounds because of the complex niche. In this study, extrusion-derived endothelial NVs were manufactured and then hybridized with rhamnolipid liposomes to obtain biomimetic hybrid nanovesicles (HNVs). The HNVs were biocompatible and achieved endothelium-targeted delivery through membrane CXCR4-mediated homologous homing. More importantly, the HNVs exhibited better penetration and antibacterial activity compared with NVs, which further promote the intrinsic endothelium targeting in infected diabetic wounds. Therefore, the present research has established a novel bioactive delivery system-HNV with enhanced targeting, penetration, and antibacterial activity-which might be an encouraging strategy for infected diabetic wound treatment.