Natural carrier-free self-assembled binary polyphenol nanoparticles remodel the gut microenvironment for inflammatory bowel disease prevention.

Developing biocompatible, multi-target therapeutics remains a critical challenge in the management of inflammatory bowel disease (IBD). Herein, we engineered a carrier-free nanoplatform (Cur-Ant NPs) via the facile self-assembly of two natural polyphenols: curcumin (Cur) and anthocyanin (Ant). Spectroscopic analysis and molecular dynamics simulations confirmed that the assembly is stabilized by robust π-π stacking and hydrogen bonding networks, yielding uniform, spherical nanostructures with integrated functionality. In a dextran sulfate sodium (DSS)-induced colitis model, orally administered Cur-Ant NPs demonstrated superior therapeutic efficacy compared to both free polyphenols and the clinical standard, sulfasalazine (SASP). The nanoparticles' potent anti-inflammatory activity was initially validated in a zebrafish model, where they effectively inhibited neutrophil infiltration and scavenged reactive oxygen species (ROS). These protective effects were further substantiated in a murine model, where multi-omics analysis revealed a tripartite mechanism of action: reinforcing the intestinal epithelial barrier, mitigating pro-inflammatory cytokine responses, and remodeling the dysbiotic gut microbiome. Our findings establish Cur-Ant NPs as a potent, safe candidate for IBD prevention and highlight a scalable, green engineering strategy for designing next-generation nanomedicines based on the supramolecular co-assembly of natural bioactive agents.