Tumor specific ultrasound enhanced gene transfer in vivo with novel liposomal bubbles.

Bubble liposomes (liposomes which entrap an ultrasound imaging gas) may constitute a unique system for delivering various molecules efficiently into mammalian cells in vitro. In this study, Bubble liposomes were compared with cationic lipid (CL)-DNA complexes as potential gene delivery carriers into tumor in vivo. The delivery of genes by Bubble liposomes depended on the intensity of the applied ultrasound. Transfection efficiency plateaued at 0.7 W/cm(2) ultrasound intensity. Bubble liposomes efficiently transferred genes into cultured cells even when the cells were exposed to ultrasound for only 1 s. In addition, Bubble liposomes could introduce the luciferase gene more effectively than CL-DNA complexes into mouse ascites tumor cells and solid tumor tissue. We conclude that the combination of Bubble liposomes and ultrasound is a minimally-invasive and tumor specific gene transfer method in vivo.

Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound.

Microbubbles and ultrasound have recently been investigated with a view to improving the transfection efficiency of non-viral gene delivery systems. However, microbubbles are unstable and their targeting ability is insufficient for clinical use. To circumvent these problems, we developed novel polyethyleneglycol (PEG) modified liposomes (Bubble liposomes) containing perfluoropropane, which is an ultrasound imaging gas. Here, we used ultrasound to induce cavitation in Bubble liposomes and then investigated their ability to deliver genes in vitro and in vivo. Bubble liposomes could deliver plasmid DNA to many cell types without cytotoxicity. Additionally, in vivo gene delivery, Bubble liposomes were more effective delivery into femoral artery than lipofection method. Thus, Bubble liposomes might be efficient and novel non-viral tools for gene delivery.