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Self-assembled RNAi nanoflowers via rolling circle transcription for aptamer-targeted siRNA delivery†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-06-07 00:00:00 , DOI: 10.1039/c8tb00758f Hui Cheng 1, 2, 3, 4, 5 , Shanni Hong 1, 2, 3, 4, 5 , Zhili Wang 1, 2, 3, 4, 5 , Na Sun 1, 2, 3, 4, 5 , Tengfei Wang 1, 2, 3, 4, 5 , Ye Zhang 1, 2, 3, 4, 5 , Hongxia Chen 5, 6, 7, 8 , Renjun Pei 1, 2, 3, 4, 5
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-06-07 00:00:00 , DOI: 10.1039/c8tb00758f Hui Cheng 1, 2, 3, 4, 5 , Shanni Hong 1, 2, 3, 4, 5 , Zhili Wang 1, 2, 3, 4, 5 , Na Sun 1, 2, 3, 4, 5 , Tengfei Wang 1, 2, 3, 4, 5 , Ye Zhang 1, 2, 3, 4, 5 , Hongxia Chen 5, 6, 7, 8 , Renjun Pei 1, 2, 3, 4, 5
Affiliation
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To deliver siRNA efficiently, prevailing conventional lipid or polymer encapsulation often needs multi-step compounding methods, which may inevitably introduce cationic or other components and may lead to cytotoxicity or an immune response. Herein, we present a novel enzymatic synthetic approach to produce tumor-targetable RNAi nanoflowers. The RNAi nanoflowers are mainly composed of multiple tandem copies of siRNA precursors by rolling circle transcription (RCT), and produce large amounts of siRNA to silence Bcl-2 gene expression after cellular uptake, which can overcome the problem of low loading capacity. In particular, the RNAi microspheres (RNAi-MS) were condensed into nanosized complexes (RNAi nanospheres, RNAi-NS) by cholesterol-modified DNA strands without the assistance of polycationic agents. RNAi-NS are entirely composed of nucleic acid, giving them lower cytotoxicity and immunogenicity, which can be caused by synthetic polycationic reagents. In addition, the RNAi nanoflowers can also integrate DNA aptamers that bind specifically to target membrane proteins for cell-targeting. Therefore, thousands of copies of siRNA will be delivered to cells specifically, and this RNAi nanoflower system will have great potential for siRNA delivery and biomedical applications.
中文翻译：
通过滚环转录 自组装的RNAi纳米花可用于适体靶向的siRNA递送†
为了有效地递送siRNA，流行的常规脂质或聚合物封装通常需要多步复合方法，这可能不可避免地引入阳离子或其他成分，并可能导致细胞毒性或免疫反应。在本文中，我们提出了一种新型的酶促合成方法来生产可靶向肿瘤的RNAi纳米花。RNAi纳米花主要通过滚环转录（RCT）由多个串联的siRNA前体拷贝组成，并在细胞摄取后产生大量的siRNA来沉默Bcl-2基因的表达，从而克服了低负荷能力的问题。特别是，无需胆固醇的修饰的DNA链，无需聚阳离子试剂的帮助，即可将RNAi微球（RNAi-MS）浓缩成纳米尺寸的复合物（RNAi纳米球，RNAi-NS）。RNAi-NS完全由核酸组成，使它们具有较低的细胞毒性和免疫原性，这可能是合成聚阳离子试剂引起的。另外，RNAi纳米花还可以整合DNA适体，该适体与靶膜蛋白特异性结合，可进行细胞靶向。因此，成千上万的siRNA拷贝将被特异地传递到细胞中，这种RNAi纳米花系统将具有巨大的潜力用于siRNA传递和生物医学应用。
更新日期：2018-06-07
中文翻译：
通过滚环转录 自组装的RNAi纳米花可用于适体靶向的siRNA递送†
为了有效地递送siRNA，流行的常规脂质或聚合物封装通常需要多步复合方法，这可能不可避免地引入阳离子或其他成分，并可能导致细胞毒性或免疫反应。在本文中，我们提出了一种新型的酶促合成方法来生产可靶向肿瘤的RNAi纳米花。RNAi纳米花主要通过滚环转录（RCT）由多个串联的siRNA前体拷贝组成，并在细胞摄取后产生大量的siRNA来沉默Bcl-2基因的表达，从而克服了低负荷能力的问题。特别是，无需胆固醇的修饰的DNA链，无需聚阳离子试剂的帮助，即可将RNAi微球（RNAi-MS）浓缩成纳米尺寸的复合物（RNAi纳米球，RNAi-NS）。RNAi-NS完全由核酸组成，使它们具有较低的细胞毒性和免疫原性，这可能是合成聚阳离子试剂引起的。另外，RNAi纳米花还可以整合DNA适体，该适体与靶膜蛋白特异性结合，可进行细胞靶向。因此，成千上万的siRNA拷贝将被特异地传递到细胞中，这种RNAi纳米花系统将具有巨大的潜力用于siRNA传递和生物医学应用。
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