Coptis chinensis-derived extracellular vesicle-like nanoparticles delivered miRNA-5106 suppresses NETs by restoring zinc homeostasis to alleviate colitis.

BACKGROUND

Inflammatory bowel disease (IBD) is a chronic disorder marked by persistent inflammation and damage to the intestinal mucosa. Despite significant advances in treatment, there remains an unmet need for more effective and safer therapeutic strategies.

RESULTS

In this study, we isolated and characterized extracellular vesicle-like nanoparticles (ELNs) derived from Coptis chinensis (Cc-ELNs) and evaluated their therapeutic potential in IBD. Intraperitoneal administration of Cc-ELNs in dextran sulfate sodium (DSS)-induced colitis mice demonstrated selective targeting of inflamed intestinal regions. Cc-ELNs significantly alleviated colitis by reducing neutrophil recruitment and inhibiting the formation of neutrophil extracellular traps (NETs). Furthermore, by suppressing NET formation, Cc-ELNs mitigated pyroptosis in intestinal epithelial cells (IECs) and promoted the proliferation of both IECs and intestinal stem cells (ISCs). Mechanistically, Cc-ELNs delivered miR-5106, which downregulated Slc39a2 expression, thereby restoring zinc homeostasis in neutrophils and reducing NET formation.

CONCLUSIONS

These findings establish Cc-ELNs as a novel, natural, and effective therapeutic candidate for IBD, highlighting the potential of plant-derived nanoparticle-based therapies.