A dual-functional nanoplatform based on pH-driven self-assembly of pea protein isolate-folic acid conjugate for targeted and stabilized delivery of curcumin

Curcumin (Cur), a bioactive flavonoid with multiple health benefits, has limited applications due to its pronounced hydrophobicity, poor stability, and lack of targeting ability. To overcome these limitations, a pH-driven self-assembly strategy was developed to construct a pea protein isolate-folic acid (PPI-FA) nano-delivery system for encapsulating Cur. The formation mechanism of PPI-FA-Cur nanocomposites involved the unfolding (at pH 12) and subsequent refolding (by adjustment to pH 7) of the protein structure, coupled with the deprotonation and protonation processes of Cur. The PPI-FA-Cur nanocomposites demonstrated a higher Cur loading capacity (66.23 μg/mg), outperforming PPI-Cur (58.79 μg/mg). The core-shell PPI-FA-Cur exhibited a uniform nanoscale size (69.67 nm), and Cur was transformed into an amorphous state within the nanocomposites. Encapsulation within PPI-FA markedly enhanced the thermal, ultraviolet, pH, and long-term storage stability of Cur. Additionally, PPI-FA demonstrated superior stability enhancement effects for Cur compared to PPI. The antioxidant capacity of PPI-FA-Cur was 1.54-fold and 1.16-fold higher than that of free Cur and PPI-Cur, respectively. Crucially, cellular uptake and in vivo fluorescence imaging experiments validated that the PPI-FA-based nano-delivery system possessed the capability to recognize cellular folate receptors, thereby enabling the targeted delivery of Cur. This work provides a plant protein-based multifunctional nanoplatform that integrates active targeting with enhanced stability for the precise delivery of hydrophobic actives.