# Targeted intracellular oral RNA delivery through tea polyphenol nanovesicle to outer membrane vesicle transfer for colitis treatment **Authors:** Taisong Fang, Songbai Liu PMC · DOI: 10.1126/sciadv.adx8336 · 2026-03-27 ## 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. ## Key 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. ## Linked entities - **Chemicals:** epigallocatechin (PubChem CID 72277), bilirubin (PubChem CID 5280352), Lys-Asp-Glu-Leu (PubChem CID 123910) - **Diseases:** colitis (MONDO:0005292) - **Species:** Escherichia coli Nissle 1917 (taxon 316435), Mus musculus (taxon 10090) ## Full-text entities - **Genes:** Fgf1 (fibroblast growth factor 1) [NCBI Gene 14164] {aka Dffrx, Fam, Fgf-1, Fgf2b, Fgfa}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Rnase1 (ribonuclease, RNase A family, 1 (pancreatic)) [NCBI Gene 19752] {aka Rib-1, Rib1}, Hspa5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 14828] {aka Bip, D2Wsu141e, D2Wsu17e, Grp78, Hsce70, SEZ-7}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Ddit3 (DNA-damage inducible transcript 3) [NCBI Gene 13198] {aka AltDDIT3, CHOP-10, CHOP10, chop, gadd153}, Ocln (occludin) [NCBI Gene 18260] {aka Ocl}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b} - **Diseases:** Colitis (MESH:D003092), necrosis (MESH:D009336), colon lengthening (MESH:D003108), gut (MESH:C536735), Inflammatory (MESH:D007249), disorders (MESH:D009358), weight gain (MESH:D015430), OMVs (MESH:D015433), UC (MESH:D003093), tissue (MESH:D017695), CD (MESH:D003424), cancer (MESH:D009369), cytotoxicity (MESH:D064420), dysbiosis (MESH:D064806), GI diseases (MESH:D005767), proinflammatory cytokines (MESH:D000080424), degenerative diseases (MESH:D019636), IBD (MESH:D015212), splenomegaly (MESH:D013163), intestinal-related diseases (MESH:D007410), EcN (MESH:D004927) - **Chemicals:** Propionic anhydride (MESH:C096126), hydrochloric acid (MESH:D006851), DSS (MESH:D016264), polyphenol (MESH:D059808), LPS (MESH:D008070), petroleum ether (MESH:C004544), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (MESH:C000613388), hematoxylin (MESH:D006416), CO2 (MESH:D002245), isopropanol (MESH:D019840), Formvar (MESH:C013215), H2O (MESH:D014867), SCFAs (MESH:D005232), sugar (MESH:D000073893), EGCG (MESH:C045651), butyrate (MESH:D002087), nitrogen (MESH:D009584), glucose (MESH:D005947), Hoechst 33342 (MESH:C017807), Tracker (MESH:C035705), formic acid (MESH:C030544), acetate (MESH:D000085), chlorpromazine (MESH:D002746), acetonitrile (MESH:C032159), succinate (MESH:D019802), paraffin (MESH:D010232), ROS (MESH:D017382), 2',7'-dichlorofluorescein diacetate (MESH:C029569), Lys (MESH:D008239), Hydroxylamine (MESH:D019811), methanol (MESH:D000432), calcein AM (MESH:C085925), bilirubin (MESH:D001663), hydrogen peroxide (MESH:D006861), H&E (MESH:D006371), DMSO (MESH:D004121), N-Hydroxysuccinimide (MESH:C001426), dichloromethane (MESH:D008752), ethyl acetate (MESH:C007650), palmitic acid (MESH:D019308), Triethylamine (MESH:C016162), alcian blue (MESH:D000423), PI (MESH:D010716), Leu (MESH:D007930), 4',6-diamidino-2-phenylindole (MESH:C007293), propidium iodide (MESH:D011419), paraformaldehyde (MESH:C003043), sodium citrate (MESH:D000077559), EDC (MESH:C024565), periodic acid (MESH:D010504), DHE (MESH:C067883), HA (MESH:D006820), TRIzol (MESH:C411644), nitrite (MESH:D009573), uranyl acetate (MESH:C005460), lipid (MESH:D008055), Pyridine (MESH:C023666), Nystatin (MESH:D009761), EGC (MESH:C057580), agarose (MESH:D012685) - **Species:** Anaerotruncus (genus) [taxon 244127], Homo sapiens (human, species) [taxon 9606], Streptococcus (genus) [taxon 1301], Mus musculus (house mouse, species) [taxon 10090], Ruminococcus (genus) [taxon 1263], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Alistipes inops (species) [taxon 1501391], Escherichia coli Nissle 1917 (strain) [taxon 316435] - **Cell lines:** /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), S23 — Mus musculus (Mouse), Hybridoma (CVCL_N330), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), HA — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_D044), S26J — Homo sapiens (Human), Hybrid cell line (CVCL_B0UB) ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13025053/full.md --- Source: https://tomesphere.com/paper/PMC13025053