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

TL;DR

A new method using tea polyphenol nanovesicles enables efficient oral RNA delivery to treat colitis by targeting inflamed intestinal cells.

Contribution

A vesicle-to-vesicle transfer strategy using tea polyphenols for targeted RNA delivery to treat colitis is introduced.

Findings

RNA encapsulated in nanovesicles was efficiently transferred to outer membrane vesicles for oral delivery.

Hybrid vesicles anchored with HA-BR-KDEL ligand targeted the endoplasmic reticulum in inflammatory intestinal cells.

Oral delivery of the hybrid vesicles significantly alleviated colitis symptoms in mice.

Abstract

Efficient oral delivery of RNA to the target site is a long-standing issue for nucleic acid–based therapy. Herein, we adopted a vesicle-to-vesicle transfer strategy and established an efficient approach to encapsulate and stabilize RNA for targeted oral delivery. The amphiphilic specifically acylated epigallocatechin directly performed encapsulation of RNA and generated nanovesicles in high efficiency without assistance of additional materials. The RNA encapsulated in the nanovesicles was efficiently transferred to outer membrane vesicles (OMVs) derived from Escherichia coli 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.

A vesicle-to-vesicle transfer strategy achieved efficient oral delivery of RNA to intracellular target site for colitis treatment.

Figures