Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound

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• 作者：Xiangyang Xie^&lowast ; ; Wen Lin^&dagger ; ; Mingyuan Li^&Dagger ; ; Yang Yang^&Dagger ; ; ^{amms2013@126.com" class="auth_mail" title="E-mail the corresponding author} ; Jianping Deng^&dagger ; ; Hui Liu^&lowast ; ; Ying Chen^&lowast ; ; Xudong Fu^&lowast ; ; Hong Liu^&lowast ; ; Yanfang Yang^§ ;
• 关键词：Ultrasound ; Nanobubbles ; Cell-penetrating peptides ; siRNA delivery
• 刊名：Ultrasound in Medicine & Biology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：42
• 期：6
• 页码：1362-1374
• 全文大小：2579 K

文摘

Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA.