siRNA delivery system using Bubble liposomes and ultrasound

Small interfering RNA (siRNA) is expected to be a novel therapeutic tool. However, a useful and practical delivery method for siRNA does not yet exist, limiting its application for disease treatment. Recently, we have developed novel polyethylene glycol-modified liposomes (Bubble liposomes) that can entrap an ultrasound imaging gas, which enables them to be used as a gene delivery tool when combined with ultrasound exposure. We therefore examined whether Bubble liposomes potentiate the delivery of siRNA. Bubble liposomes combined with ultrasound exposure efficiently delivered siRNA within a short time in vitro, resulting in specific gene-silencing effects without endocytosis. The local delivery of siRNA with Bubble liposomes and ultrasound also showed a gene-silencing effect in vivo. To control the biodistribution of both Bubble liposomes and siRNA, we further developed novel cholesterol-conjugated siRNA (chol-siRNA)-loaded Bubble liposomes (chol-si-BLs), which make siRNA stable even in the presence of RNase. This specific gene-silencing effect was also achieved by transfection with chol-si-BLs and ultrasound. Thus, the combination of chol-si-BLs with ultrasound exposure is expected to deliver siRNA into a specific tissue via systemic injection. In this review, we discuss the ultrasound-mediated siRNA delivery systems combined with Bubble liposomes and their potential utility as a non-viral vector system.