Conjugation of membrane-destabilizing peptide onto gelatin–siloxane nanoparticles for efficient gene expression

One of the crucial steps in gene delivery with non-viral vectors is the escape of DNA complexes from the endosome. In order to improve gene transfection efficiency, we designed a novel gene delivery vector gelatin–siloxane nanoparticles (GS NPs) conjugated with two different membrane-destabilizing peptides, octaarginine (R8) and a subunit of influenza virus haemagglutinin HA2. Both R8-GS NPs and HA2-GS NPs had high positive surface charges. They could condense and protect DNA against serum/DNase degradation. Results from flow cytometry and confocal laser scanning microscope respectively indicated that R8-GS NPs had higher uptake efficiency than HA2-GS NPs, whereas HA2-GS had higher endosome escaping efficiency. Furthermore, in vitro transfection displayed a higher gene expression level with HA2-modified GS NPs, which suggested that endosome escaping is the crucial step for nanoparticle mediated gene therapy.