Dual functionalization of Lactobacillus helveticus-derived exosomes with mannose and cRGD (McRLHexo) improved membrane lipid ordering, stability, and pterostilbene loading, and enabled dual-targeted epithelial translocation and macrophage targeting, so that McRLHexo@PTS markedly alleviated DSS-induced colitis in mice.
Dual functionalization of L. helveticus exosomes with mannose and cRGD changed their membrane organization and surface structure.
McRLHexo was more stable than unmodified exosomes under UV, thermal, and digestive conditions.
McRLHexo increased loading of pterostilbene (PTS).
McRLHexo@PTS crossed the epithelium efficiently via cRGD-integrin pathways.
McRLHexo@PTS targeted macrophages through mannose/cRGD dual recognition.
In DSS-induced colitis mice, McRLHexo showed optimal accumulation and uptake in the colon.
McRLHexo@PTS markedly alleviated DSS-induced colitis in mice.
The study presents a dual-targeted probiotic exosome platform for oral therapy.
This study worked on improving tiny natural vesicles (exosomes) released by the probiotic bacterium Lactobacillus helveticus so they can carry a plant compound, pterostilbene, through the gut to inflamed tissue. The researchers attached two targeting molecules, mannose and cRGD, to the surface of the vesicles. This made the vesicle membrane more orderly and gave it a denser protective coating, and it let the vesicles hold more pterostilbene. The modified vesicles held up better against UV light, heat, and simulated digestion, retaining more than 86% of their cargo under digestive conditions. In cell experiments they crossed the gut lining through an integrin-related uptake route and were picked up by immune cells called macrophages through both targeting molecules. In mice with chemically induced colitis, the modified vesicles accumulated best in the colon. When loaded with pterostilbene, they restored body weight, colon length, and gut lining integrity, and lowered inflammation and oxidative stress. This research suggests that engineering the surface of probiotic-derived vesicles could be a route to oral delivery of anti-inflammatory compounds directly to the inflamed gut. The results come from cell and mouse models, so whether this works in people has not been shown.
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Upload Your LabsJi Q, Meng R, Wu S, Feng R, Zhang B. (2026). Mannose-cRGD Engineered Lactobacillus helveticus-Derived Exosomes Enhance Loaded Pterostilbene Bioavailability: From Dual Insights of Membrane Lipid Orderliness and Dual-Targeting Endocytosis Modulation.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.5c16503