Obeid Mohammad A, Elburi Ashref, Young Louise C, Mullen Alexander B, Tate Rothwelle J, Ferro Valerie A
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street, G4 0RE Glasgow, United Kingdom.
Faculty of Pharmacy, Yarmouk University , Irbid, Jordan.
Mol Pharm. 2017 Jul 3;14(7):2450-2458. doi: 10.1021/acs.molpharmaceut.7b00352. Epub 2017 Jun 8.
Small interfering RNAs (siRNA) have a broad potential as therapeutic agents to reversibly silence any target gene of interest. The clinical application of siRNA requires the use of safe and effective delivery systems. In this study, we investigated the use of nonionic surfactant vesicles (NISV) for the delivery of siRNA. Different types of NISV formulations were synthesized by microfluidic mixing and then evaluated for their physiochemical properties and cytotoxicity. The ability of the NISV to carry and transfect siRNA targeting green fluorescent protein (GFP) into A549 that stably express GFP (copGFP-A549) was evaluated. Flow cytometry and Western blotting were used to study the GFP expression knockdown, and significant knockdown was observed as a result of siRNA delivery to the cells by NISV. This occurred in particular when using Tween 85, which was able to achieve more than 70% GFP knockdown. NISV were thus demonstrated to provide a promising and effective platform for therapeutic delivery of siRNA.
小干扰RNA(siRNA)作为治疗药物具有广泛的潜力,可用于可逆性沉默任何感兴趣的靶基因。siRNA的临床应用需要使用安全有效的递送系统。在本研究中,我们研究了使用非离子表面活性剂囊泡(NISV)递送siRNA。通过微流体混合合成了不同类型的NISV制剂,然后评估其理化性质和细胞毒性。评估了NISV将靶向绿色荧光蛋白(GFP)的siRNA携带并转染到稳定表达GFP的A549细胞(copGFP-A549)中的能力。使用流式细胞术和蛋白质印迹法研究GFP表达的敲低情况,结果发现通过NISV将siRNA递送至细胞后,观察到了显著的敲低。特别是在使用吐温85时,这种情况尤为明显,它能够实现超过70%的GFP敲低。因此,NISV被证明为siRNA的治疗递送提供了一个有前景且有效的平台。