Effect of molecular weight of polysaccharide on efficient plasmid DNA delivery by polyethylenimine-polysaccharide-Fe(III) complexes

Polyethylenimine (PEI) is considered as the gold standard for evaluating non-viral gene vectors due to its proton sponge effect and high transfection efficiency. However, its cytotoxicity limits its application. Rice bran polysaccharide (RBP) is rich in nature and beneficial for preparation of biodegradable biomaterials. In this work, three PEI modified RBP-Fe complexes (PIP-1, PIP-2, and PIP-3) were prepared based on RBP with different molecular weight (M-w). Then the potential of PIP complexes for plasmid DNA (pDNA) delivery and the influence of M-w was studied. PIP complexes showed better safety and higher gene transfection efficiency than PEI. PIP-1 was prepared by RBP with lower M-w and could formed PIP-1/pDNA nanoparticle with lower particle size which exhibited higher gene transfection efficiency than other PIP complexes prepared by RBP with higher M-w. The results indicate that the PIP/pDNA complex exhibits a multi-pathway cellular uptake mechanism. Clathrin dependent and caveolin dependent endocytosis and macropinocytosis were involved in the cellular uptake process of PIP/pDNA complex. It is hoped that this study can provide useful enlightenment for the research and development of gene vector based on polysaccharide.