Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound

Delivery of siRNA into the cytoplasm by liposomal bubbles and ultrasound
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DOI:
10.1016/j.jconrel.2008.08.019
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发表时间:
2008-12-08
影响因子:
10.8
通讯作者:
Aramaki, Yukihiko
Aramaki, Yukihiko
中科院分区:
医学1区
文献类型:
--
作者:
Negishi, Yoichi;Endo, Yoko;Aramaki, Yukihiko

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小干扰RNA(siRNA)有望成为一种新型的治疗工具,但其应用受到低效率递送系统的限制。最近,我们已经开发了新型聚乙二醇修饰的脂质体(气泡脂质体; BL)截留超声(US)成像气体,它可以作为基因递送工具与US曝光。在这项研究中,我们研究了BL是否适合siRNA的递送。BL在体外仅暴露于US 10秒就有效地递送siRNA。特异性基因沉默效应甚至可以在血清存在或内吞作用被破坏的情况下很好地实现。我们认为,siRNA是直接引入细胞质的BL和US和机制,使有效的转染在短时间内,在高血清的存在下。还进行了用BL和US将siRNA转染到胫骨肌中。基因沉默效应可持续3周以上。因此,BL可能是一种有用的siRNA递送工具,在体外和体内。(C)2008 Elsevier B. V.保留所有权利。
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. (C) 2008 Elsevier B.V. All rights reserved.