Abstract

Inflammatory bowel disease (IBD) emerges from a self-reinforcing triad of epithelial barrier failure, oxidative stress, and immune dysregulation, while concomitants dysbiosis amplifies mucosal inflammation and-via the gut-joint axis-drives systemic autoimmunity such as rheumatoid arthritis (RA). Here, we report a triple-action multilayer oral nanoplatform, LBL-BM, that co-delivers berberine (BBR), myricetin (MYR), and TNF-α-targeting small interfering RNA (siTNF-α). A chitosan/siTNF-α/alginate shell over a supramolecular BBR/MYR core overcomes gastrointestinal instability, poor lesion targeting, and fleeting siRNA exposure, enabling redox control and epithelial support coupled with pro-inflammatory cytokine silencing. This platform reduces reactive oxygen species (ROS), attenuates oxidative injury and apoptosis, and preserves tight-junction proteins. In dextran sulfate sodium (DSS)-induced colitis, it significantly improves clinical and histological outcomes, skews macrophage polarization toward an M2 phenotype, and reprograms the microbiota toward short-chain fatty acids (SCFAs)-associated, inflammation-attenuating communities. Consistent with modulation of the gut–joint axis, benefits extended beyond the intestine: in collagen antibody-induced arthritis (CAIA) it lowers clinical scores and paw swelling, attenuates synovitis and bone erosion, preserves cartilage, and reduces systemic cytokines (TNF-α, IL-17A, and IL-1β). Collectively, these findings establish LBL-BM as a multifunctional oral nanomedicine that restores intestinal homeostasis and holds translational promise for treating both IBD and RA.

文章链接：https://doi.org/10.1016/j.apsb.2026.08.021

文章导读：https://mp.weixin.qq.com/s/bhXgNKgpD8-I5xAl01CxQw