Self-assembly non-covalent binding mechanism of lycopene-protein-chondroitin sulfate ternary nanoparticles: Multidimensional characterization and molecular dynamics simulation.

To overcome lycopene's (LYC's) poor water solubility, oxidative instability, and low bioaccessibility, chondroitin sulfate (CS) was used as a stabilizing layer to construct LYC-Protein-CS nanoparticles (LYC-Protein-CS NPs) using different proteins. Their structures and delivery performance were compared to clarify how protein structure influences the delivery of lipophilic bioactives. Zein's layered folding and hydrophobic-hydrophilic partitioning promoted assembly with CS, forming a compact core-shell network. Consequently, LYC-Zein-CS showed superior encapsulation, dispersion stability, antioxidant activity, and gastrointestinal release behavior. Compared with free LYC, this system increased apparent bioaccessibility by 12.95-fold in the gastric phase and 14.87-fold in the intestinal phase during simulated digestion. These findings reveal how protein structural differences regulate the performance of protein-polysaccharide nanoparticles and provide theoretical and technical insights into the precise design and practical application of delivery systems for LYC and other lipophilic bioactive compounds.