Dual‐Carriers of Tartary Buckwheat‐Derived Exosome‐Like Nanovesicles Synergistically Regulate Glucose Metabolism in the Intestine‐Liver Axis

The utilization of plant-derived exosome-like nanovesicles (ELNs) as nanocarriers for oral delivery of bioactives has garnered significant attention. However, their distinctive lipid membrane composition may result in elevated membrane permeability within the gastrointestinal environment, leading to the leakage of carried bioactives. Inspired by the concept of projectile design, Tartary buckwheat-derived ELNs (TB-ELNs) based dual-carriers are fabricated by loading chlorogenic acid (CGA) into the cores and bonding selenium nanoparticles (SeNPs) to the lipid membrane. The results indicate that SeNPs bond markedly augments the membrane rigidity, and therefore enhances the stability of TB-ELNs and the retention rate of the loaded CGA during gastrointestinal digestion. In vitro and in vivo studies indicates that the TB-ELNs based dual-carriers are internalized by epithelial cells and transcytosis via the endoplasmic reticulum, and show the synergistic regulatory effect on high-fat diet-induced hyperglycemia in the intestine-liver axis. These results may be attributed to the fact that SeNPs combination reduces the gastrointestinal degradation of the carried bioactives. Moreover, SeNPs with antioxidant property can protect ELNs and their carried bioactives from oxidative damage, thereby enhancing their biological activities. Collectively, this study offers a new strategy to develop highly efficient oral delivery systems for bioactives to alleviate hyperglycemia and diabetes.