Effective gene delivery with liposomal bubbles and ultrasound as novel non-viral system

Abstract

We developed the novel liposomal bubbles (Bubble liposomes) containing ultrasound imaging gas, perfluoropropane. Bubble liposomes were made of pegylated liposomes and were smaller than conventional microbubbles. Bubble liposomes also had a function as imaging agents in cardiosonography. In addition, Bubble liposomes could deliver plasmid DNA into various types of cells in vitro without cytotoxicity by the combination of ultrasound. In vivo gene delivery, Bubble liposomes could deliver plasmid DNA into mouse femoral artery by the transdermally exposure of ultrasound. This transfection efficiency was more effectively than lipofection method. Interestingly, the gene expression was only observed at the site of ultrasound exposure. Therefore, we concluded that Bubble liposomes could be good tools to establish tissue-specific gene delivery system as well as ultrasound imaging agents.

Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles targeting activated platelet glycoprotein IIb/IIIa complex—in vitro and in vivo study

“…This is also the first study to show the feasibility of perfluorocarbon gas-containing liposomes, rather than a phospholipid mono-layer, as a targeted ultrasound contrast agent, in addition to a carrier for gene delivery [11][12][13].…”

“…We have developed novel polyethylene glycol-modified liposomal bubbles (bubble liposomes, BL) containing perfluoropropane gas, which can be used as an ultrasound contrast agent [11][12][13]. We attached targeted ligands for activated platelets to these BL.…”

Nonviral Gene Delivery Systems by the Combination of Bubble Liposomes and Ultrasound

“…Since this approach can be used to deliver extracellular material such as genes into cells, microbubbles could facilitate US-mediated gene delivery. In addition, submicron-sized bubbles (nanobubbles), which are smaller than conventional microbubbles, were recently reported (Gao, Kennedy, Christensen, & Rapoport, 2008;Wang, Li, Zhou, Huang, & Xu, 2010), and we have developed novel liposomal nanobubbles (bubble liposomes (BLs)) Suzuki et al, 2009Suzuki, Takizawa, Kuwata, et al, 2008;Suzuki, Takizawa, Negishi, et al, 2008;Suzuki, Takizawa, Negishi, Hagisawa, et al, 2007;Suzuki, Takizawa, Negishi, Utoguchi, et al, 2007;Un et al, 2010;Yamashita et al, 2007). These nanobubbles can also be used to enhance the efficiency of US-mediated gene delivery.…”

Low-Intensity Ultrasound Promotes Clathrin-Dependent Endocytosis for Drug Penetration into Tumor Cells

“…The ability of ultrasound to heat tissue deep inside the body can be used to control transgene expression when the gene is placed under the control of a heat-sensitive promoter (Moonen 2007). Mild (43 C) or intense (with high-intensity focused ultrasound) hyperthermia is used to warm drugs and tissues (Draper et al 1995;Escoffre et al 2013;Paparel et al 2008) to increase the penetration of drugs, liposome-encapsulated drugs and genes into cells and tissues (Lawrie et al 2000;Rifai et al 2010;Suzuki et al 2007). These applications have been performed in various tissues such as cardiac, tumor, bone and even fetal tissue.…”