Surface modification of RNA nanoparticles by ionic interaction for efficient cellular uptake
Surface modification of RNA nanoparticles by ionic interaction for efficient cellular uptake
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DOI：
10.1016/j.jiec.2018.10.013
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发表时间：
2019-02-25
影响因子：
6.1
通讯作者：
Lee, Jong Bum
中科院分区：
文献类型：
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作者：
Jeon, Hyunsu;Han, Sangwoo;Lee, Jong Bum
小干扰RNA（siRNA）介导的靶蛋白特异性调控已受到广泛关注。然而，它受到了裸RNA固有的不稳定性的挑战。为了解决这个问题，已经开发了多种siRNA递送方法。通过互补滚环转录（cRCT）合成的RNA纳米颗粒（RNP）由于其在血清条件下的稳定性增强以及适合增强渗透和保留（EPR）效应的尺寸而被引入作为siRNA递送的新途径。然而，由于RNA的先天结构，RNP带负电荷，导致在不使用转染剂的情况下细胞摄取效率低下。本文报道了一种简单的钙离子表面改性RNP的方法。生成钙层RNA纳米颗粒（CaRNP）并用于证明siRNA递送到体外HeLa细胞的增强的效率。结果表明，这种简单的方法可以提高RNP的细胞摄取效率相比，裸RNP。此外，该方法也适用于其他类型的RNA，如信使RNA（mRNA）、微小RNA（miRNA）或单向导RNA（sgRNA），这将大大增强RNP的治疗潜力。(C)2018年韩国工业与工程化学学会。Elsevier B.V.出版，保留所有权利。
Small interference RNA (siRNA) delivery has gained much attention for specific regulation of target protein via RNA interference. However, it has been challenged by inherent instability of naked RNA. To address this issue, a variety of siRNA delivery methods have been developed. The synthesis of RNA nanoparticles (RNPs) by complementary rolling circle transcription (cRCT) has been introduced as a novel route for siRNA delivery, because of the enhanced stability in serum condition and the suitable size for enhanced permeation and retention (EPR) effect. However, RNPs are negatively charged due to the innate structure of RNA, resulting in an inefficient cellular uptake without using transfection agents. In this paper, we report a simple surface modification method of RNP with calcium ion. Calcium-layered RNA nanoparticles (CaRNPs) were generated and used to demonstrate enhanced efficiency of siRNA delivery to HeLa cells in vitro. The results revealed that this simple approach could enhance the cellular uptake efficiency of RNPs in contrast to the naked RNP. Moreover, this method is also applicable for other types of RNAs such as messenger RNA (mRNA), microRNA (miRNA), or single guide RNA (sgRNA), which will greatly enhance therapeutic potential of RNPs. (C) 2018 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.