Casein-quaternary chitosan complexes induced the soft assembly of egg white peptide and curcumin for ulcerative colitis alleviation.

Soft assembly of peptide and curcumin (Cur) molecules enables functional integration by finding dynamic equilibrium states through non-covalent interactions. Herein, we developed two soft assembly systems, curcumin-egg white peptides (Cur-EWP) aggregations (AGs) and Cur-EWP-casein-quaternary chitosan (Cur-EWP-CA-QC) nanoparticles (NPs) to comparatively investigate their therapeutic effects on ulcerative colitis in mice and elucidate their underlying mechanism. Results revealed that Cur-EWP AGs, despite gastrointestinal tract instability, exhibited a propensity for swift accumulation within the colorectal region, enriching mucus-associated and short-chain fatty acid (SCAF)-producing bacteria, restoring the intestinal barrier damage. Whereas, Cur-EWP-CA-QC NPs, benefiting from their remarkable stability and exceptional mucosal adsorption properties, not only enhanced permeability of Cur and EWP in the small intestine to activate the immune response and boost tight junction protein expression but also, in their unabsorbed state, regulated the intestinal flora, exerting potent anti-inflammatory activity. Soft assembly of peptides and hydrophobic nutraceuticals could synergize biological activities to modulate chronic diseases.