Dual-functional tea polyphenol-serotonin nanoparticles for integrated inflammation suppression and mucosal repair in inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD) is a chronic and relapsing gastrointestinal disorder marked by persistent inflammation and disruption of the intestinal barrier. Current treatments often focus solely on inflammation control and lack effective mucosal repair capabilities, leading to suboptimal outcomes and adverse effects. To address this, we developed tea polyphenol and serotonin nanoparticles (TPSNs) through oxidative copolymerization of epigallocatechin gallate (EGCG) and serotonin (5-HT), combining the anti-inflammatory, antioxidant, and mucosal repair functions of both components. The therapeutic efficacy was systematically evaluated in dextran sulfate sodium (DSS)-induced acute colitis models in both zebrafish and mice, as well as in IL-10 knockout mice models of chronic colitis. Mechanistic studies revealed that TPSNs effectively scavenged reactive oxygen and nitrogen species (RONS), promoted M1-to-M2 macrophage repolarization, inhibited pyroptosis and NF-κB signaling, and activated MAPK and PI3K-AKT pathways to enhance epithelial cell proliferation and migration. TPSNs were further incorporated into a thermosensitive in situ forming gel for rectal delivery to enhance localized and sustained drug release. In vivo administration demonstrated significant amelioration of disease symptoms and histopathological features, while biosafety assessments confirmed no considerable toxicity to major organs or disruption of liver and kidney function. These findings highlight TPSNs as a safe and effective nanotherapeutic candidate for integrated IBD treatment by addressing inflammatory and mucosal repair pathways.