Negishi Yoichi, Endo Yoko, Fukuyama Tetsuya, Suzuki Ryo, Takizawa Tomoko, Omata Daiki, Maruyama Kazuo, Aramaki Yukihiko
Department of Drug and Gene Delivery System, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
J Control Release. 2008 Dec 8;132(2):124-30. doi: 10.1016/j.jconrel.2008.08.019. Epub 2008 Sep 7.
Small interfering RNA (siRNA) is expected to be a novel therapeutic tool, however, its utilization has been limited by inefficient delivery systems. Recently, we have developed novel polyethyleneglycol modified liposomes (Bubble liposomes; BL) entrapping an ultrasound (US) imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated whether the BL were suitable for the delivery of siRNA. BL efficiently delivered siRNA with only 10 s of exposure to US in vitro. Specific gene silencing effects could be achieved well even in the presence of serum or with the disruption of endocytosis. We suggest that siRNA is directly introduced into the cytoplasm by the BL and US and the mechanism enables effective transfection within a short time and in the presence of high serum. Transfection of siRNA into the tibialis muscles with BL and US was also performed. The gene-silencing effect could be sustained for more than 3 weeks. Thus, BL could be a useful siRNA delivery tool in vitro and in vivo.
小干扰RNA（siRNA）有望成为一种新型治疗工具，然而，其应用一直受到低效递送系统的限制。最近，我们开发了一种新型的聚乙二醇修饰脂质体（气泡脂质体；BL），其包裹着一种超声（US）成像气体，在超声照射下可作为基因递送工具。在本研究中，我们调查了BL是否适合递送siRNA。在体外，BL仅需10秒的超声照射就能有效地递送siRNA。即使存在血清或内吞作用被破坏，也能很好地实现特异性基因沉默效果。我们认为，siRNA通过BL和超声被直接导入细胞质，该机制能够在短时间内且在高血清存在的情况下实现有效的转染。还进行了用BL和超声将siRNA转染到胫前肌中的实验。基因沉默效果可持续超过3周。因此，BL在体外和体内都可能是一种有用的siRNA递送工具。
