Targeted intracellular oral RNA delivery through tea polyphenol nanovesicle to outer membrane vesicle transfer for colitis treatment

Nissle 1917 probiotic through membrane fusion with simple operation. The derived hybrid vesicles (HVs) were further anchored with bilirubin and Lys-Asp-Glu-Leu grafted hyaluronic acid (HA-BR-KDEL) ligand for sequential cellular and intracellular targeting to the endoplasmic reticulum of inflammatory cells in inflamed intestinal tract. Oral delivery of HVs@HA-BR-KDEL notably alleviated colitis symptoms in mice and contributed to the restoration of intestinal homeostasis. The tea polyphenol hybrid OMV strategy holds great promise for oral gene-mediated treatment.