Polysaccharide nanogel gene delivery system with endosome-escaping function: Co-delivery of plasmid DNA and phospholipase A2

We developed a novel gene delivery system capable of endosome disruption using a polysaccharide-based cationic nanogel composed of a hexadecyl group-bearing cationic cycloamylose nanogel (C16-catCA nanogel) and phospholipaseA2 (PLA2) to hydrolyze membrane phospholipids. C16-catCA nanogel formed nanoparticles with PLA2 and pDNA by hydrophobic and electrostatic interactions. Both pDNA and PLA2 were effectively internalized into cells by the C16-catCA nanogel. In addition, the pDNA expression level was enhanced when complexed with specific concentrations of PLA2. PLA2 complexed with C16-catCA nanogel also showed a similar hemolytic activity against red blood cells to that observed using native PLA2. These results suggest that the C16-catCA nanogel/PLA2 complex possesses membrane disruption ability when delivered into cells and triggers the subsequent release of pDNA from the endosome to the cytoplasm. This is the first report of co-delivery of pDNA and PLA2 using the same carrier to achieve effective gene delivery.

Graphical AbstractCo-delivery of pDNA and lipolytic enzyme (phospholipaseA2) by hydrophobized polysaccharide nanogel carrier (C16-catCA nanogel) enhanced transfection efficiency.Figure optionsDownload as PowerPoint slide