Extracellular vesicles as delivery platforms for metabolic reprogramming in skin diseases

Skin homeostasis relies on tightly coordinated metabolic networks, and metabolic dysregulation is recognized as a central contributor to various dermatological disorders. While current therapeutic strategies predominantly target disease manifestations or inflammatory pathways, targeted metabolic intervention has emerged as a promising approach in dermatology. Extracellular vesicles (EVs) serve as versatile nanoscale delivery platforms that efficiently transport therapeutic payloads to specific cutaneous cell populations, enabling precise metabolic interventions. This review systematically summarizes the metabolic alterations underlying major skin diseases. It also examines how EV-based systems deliver functional payloads, including regulatory nucleic acids, metabolic enzymes, and bioactive metabolites, to correct these disturbances. Particular emphasis is placed on the modulation of four core metabolic hubs: glucose metabolism, mitochondrial bioenergetics, lipid homeostasis, and amino acid metabolism. Through EV-mediated interventions, the pathological microenvironment may be modulated, contributing to multiple therapeutic outcomes, including inflammation resolution, accelerated tissue repair, barrier restoration, anti-fibrotic extracellular matrix (ECM) remodeling, and reversal of senescence. Current preclinical and emerging clinical studies are also critically evaluated, highlighting key translational challenges and future opportunities. Future efforts integrating dynamic metabolic profiling and rigorous bioengineering will be critical to realizing the clinical potential of EV-based dermatological therapies.