Chondroitin sulfate deposited on foxtail millet prolamin/caseinate nanoparticles to improve physicochemical properties and enhance cancer therapeutic effects

Abstract

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.