Fabrication of zein-based hydrophilic nanoparticles for efficient gene delivery by layer-by-layer assembly

As a natural biological macromolecule, zein has broad application prospects in drug delivery due to its unique self-assembly properties. In this work, zein/sodium alginate (Zein/SA) nanocomposites were prepared by a pH-cycle method, Then Zein/SA/PEI (ZSP) nanocomposites were prepared by efficient layer-by-layer assembly method, ZSP nanocomposite of higher transfection performance was further labeled by folic acid (FA). After characterizing the physicochemical properties of ZSP by various methods, the potential of ZSP as a gene delivery vehicle was explored in vitro. The results showed that ZSP had good dispersibility and stability, the diameter distribution was in the range of 124-203 nm, and it had a typical core-shell structure, which could effectively condensate DNA and protect it from nuclease hydrolysis. ZSP exhibited proton buffering capacity similar to PEI, lower cellular toxicity, lower protein adsorption and erythrocyte hemolysis effect than PEI. ZSP/pDNA complexes could be taken up by cells and exhibited higher transfection efficiency than PEI/DNA complexes at the same weight ratio. The transfection efficiency of the complex in HeLa and 293T cells can be improved by FA labeling, especially in HeLa cells. These results provide new perspective for the design and development of efficient zein-based gene delivery systems.