In this study, curcumin (Cur)-loaded chondroitin sulfate (CS)-sodium caseinate (NaCas)-stabilized foxtail millet prolamin (FP) composite nanoparticles (NPs) were fabricated via a one-pot process. FP is capable of self-assembly via liquid antisolvent precipitation under neutral and alkaline conditions (pH 7.0-11.0). Under this condition, the microstructures of hydrophobic FP cores, amphiphilic NaCas and hydrophilic CS shells were fabricated readily by a one-pot method. With an optimal FP/NaCas/CS weight ratio of 3 : 2 : 4, FP-NaCas-CS NPs shared globular microstructures at about 145 nm, and hydrophobic interactions, electrostatic forces, and hydrogen bonds were the main driving forces for the formation and maintenance of stable FP-NaCas-CS NPs. CS coating enhanced the pH stability but reduced the ionic strength stability. The formed NPs were stable over a wide pH range from 2.0 to 8.0 and elevated salt concentrations from 0 to 3 mol L-1 NaCl. FP-NaCas-CS NPs exhibited a higher Cur encapsulation efficiency of 93.4% and re-dispersion capability after lyophilization. Moreover, CS coating promoted selective accumulation in CD44-overexpressing HepG2 cells, resulting in higher inhibition of tumor growth compared to free Cur and FP-NaCas NP-encapsulated Cur. As for comparison, encapsulated Cur exhibited reduced cytotoxicity on normal liver cells L-O2. This preclinical study suggests that FP-NaCas-CS NPs could be very beneficial in terms of encapsulating hydrophobic drugs, improving the effectiveness of cancer therapies and reducing side effects on normal tissues.
