Surface Functionalized Multicomponent Envelope Type Nanosystems for Improved Gene Delivery

D. Pozzi, V. Orlando, G. Augusti Tocco, S. Biagioni, F. Cardarelli, A. Bifone, G. Caraccioloa
Sapienza University of Rome, IT

Keywords: gene delivery, lipids, multicomponent, nanosystems


Recently, a new programmed packaging strategy in which various “soft devices” that control intracellular trafficking are incorporated into single nanoparticles has been proposed. Here we apply such a novel concept to develop multicomponent envelope-type nanosystems (MENS) for overcoming intracellular membrane barriers. MENS was made of a plasmid DNA core condensed with protamine sulphate (P). The pre-assembled P/DNA core was coated by multicomponent anionic liposomes (M) and finally were surface-functionalized with poly-L-arginine, poly-L-lysine and low molecular weight chitosan. The cellular uptake mechanisms and final intracellular fate of MENS were investigated by a combination of pharmacological and imaging approaches. Remarkably, a clear correlation between surface functionalization and transfection mechanisms was found. When MENS were given to HEK 293 cells they efficiently delivered DNA and were completely not cytotoxic. Our results indicate that (i) MENS are promising transfection candidates and that (ii) surface functionalization of MENS needs to be carefully considered for the rational design of improved gene delivery system.