Endogenously modified multi-bioresponsive silk fibroin nanoparticles enhancing the cellular delivery and...

Hydrophobic bioactives such as curcumin suffer from poor aqueous solubility, low bioaccessibility, and targeting capability. In this study, silk fibroin, a natural macromolecular protein, was used to form self-assembled nanoparticles. These nanoparticles were surface-grafted with bile acids to modulate interfacial properties and exploit endogenous bile acid transport pathways for ileum-targeted curcumin delivery. Cholic acid, deoxycholic acid, and glycocholic acid were covalently grafted onto silk fibroin nanoparticles to tailor surface hydrophobicity and charge. Spectroscopic and physicochemical analyses confirmed surface modification. Deoxycholic acid grafted nanoparticles exhibited superior cellular uptake in Caco-2 cells and enhanced anti-inflammatory activity. These nanoparticles exhibited responsiveness to H₂O₂, GSH, and pH. Moreover, the nanoparticles were incorporated into an alginate-based pH-responsive hydrogel that preserved structural integrity and bioactivity during simulated digestion. In vivo evaluation further confirmed the favorable biocompatibility of the delivery system. This approach shows promise for hydrophobic bioactive compound delivery in functional foods.