Engineered plant-derived extracellular vesicles for targeted regulation and treatment of colitis-associated inflammation.

ABSTRACT

Rationale Inflammatory bowel disease (IBD) is a chronic disorder characterized by persistent inflammation of the gastrointestinal tract. Due to the elusive causes and complex mechanisms of this disorder, the development of highly effective therapeutic drugs is crucial. Extracellular vesicles (EVs) are small membrane-bound structures released by cells into the surrounding environment. Recent research has witnessed a substantial surge in the utilization of plant-derived EVs that offer advantages such as high productivity, low production costs, diverse biological functions, and low cytotoxicity. Herein, Red cabbage-derived EVs (Rabex) were investigated and engineered as potential therapeutic agents for IBD. Methods: Rabex was engineered by surface conjugation with hyaluronic acid (t-Rabex) to simultaneously enhance the targeting of intestinal epithelial and immune cells, thereby improving their therapeutic targeting and efficacy. The properties and therapeutic potential of t-Rabex were assessed through both in vitro studies and in vivo experiments, focusing on their capacity to reach the gastrointestinal tract and exert a therapeutic effect compared to unmodified Rabex. Results: Rabex exhibited dual functions, including the suppression of inflammation in macrophages and promotion of colon epithelial cell regeneration, both of which are critical for effective IBD treatment. In vitro and in vivo studies of t-Rabex have demonstrated its superior targeting efficiency to the gastrointestinal tract and therapeutic efficacy compared to Rabex, making it a promising and more effective IBD treatment. Understanding the mechanism of action of t-Rabex in colonic tissues highlighted its anti-inflammatory, antioxidative, and tight-junction maintenance properties. Conclusions: These findings underscore the potential of t-Rabex as a precise therapeutic agent for IBD and shed light on the diverse applications of plant-derived EVs.