Received for publication March 24, 2006.
Revised April 27, 2006.
Accepted for publication April 28, 2006.

Efficient Gene Transfer into Macrophages and Dendritic Cells by in Vivo Gene Delivery with Mannosylated Lipoplex via the Intraperitoneal Route

Abstract

In this study, we developed an antigen presenting cells (APCs) selective intraperitoneal gene delivery system with mannosylated cationic liposomes (Man- liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than lipoplex or naked pCMV-Luc after intraperitoneal administration and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after intraperitoneal administration was significantly higher than that after intravenous gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the intraperitoneal route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80⁺ and CD11c⁺ cells in the spleen. These results show that gene delivery with Man-liposomes via the intraperitoneal route could be an effective approach for APC-selective gene transfection.

Key words: DNA vaccine, Dendritic cells, Drug delivery system, Gene delivery, Non-viral vectors, Targeting