Engineered Microalgal Extracellular Vesicles for Enhancing Mitochondrial Homeostasis in Radiodermatitis Prevention

(SP) and engineered them by loading astaxanthin (AST) into SP-EVs, resulting in the formation of SP-EVs@AST. This engineered system significantly enhanced the solubility and stability of AST while preserving the structural integrity and biological activity of SP-EVs, thereby enabling the complementary and synergistic effects of AST and SP-EVs. SP-EVs@AST demonstrated protective effects against radiation-induced cellular damage by alleviating oxidative stress, restoring mitochondrial function, and reducing inflammatory responses. To optimize topical administration, SP-EVs@AST were incorporated into a self-assembled hydrogel composed of aldehyde-functionalized hyaluronic acid (HA-CHO) and carboxymethyl chitosan (CMCS), forming a skin radiation protection dressing (SP-EVs@AST gel). This dressing effectively preserved the activity of SP-EVs@AST, facilitated its sustained release, protected the skin from progressive radiation-induced injury, and exhibited long-term biological safety. This system demonstrates the potential of engineered microalgal EVs as carriers for poorly soluble drugs, offering a promising strategy to expand their application as a targeted drug delivery platform in biomedical fields.