Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery
Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery
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DOI：
10.1016/j.jcis.2012.09.033
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发表时间：
2013-01-15
影响因子：
9.9
通讯作者：
Xu, Zhi Ping
中科院分区：
文献类型：
--
作者：
Chen, Min;Cooper, Helen M.;Xu, Zhi Ping
小干扰 RNA (siRNA) 是治疗多种疾病的一类潜在强大的新型药物。然而，未受保护的 si RNA 的递送是无效的，因为它们在生理条件下容易被普遍存在的核酸酶降解。层状双氢氧化物纳米颗粒（LDH）已被发现是阴离子药物和核酸的有效载体。我们之前的研究表明，LDH（Z 平均粒径约为 110 nm）可以介导哺乳动物细胞中的 siRNA 传递，从而导致基因沉默。然而，短双链核酸大多吸附在外表面，并没有得到LDH的良好保护。为了增强 siRNA 嵌入 LDH 夹层以及后续 siRNA 递送的效率，我们通过工程化的非水方法制备了更小的 LDH（Z 平均粒径约为 45 nm）。我们在此证明，dsDNA/siRNA 可以更有效地嵌入这些小的 LDH 纳米颗粒中，更多的 dsDNA/siRNA 可以转染到 HEK 293T 细胞中，并且使用更小的 LDH 可以实现更有效的靶基因沉默。因此，较小的 LDH 颗粒作为 RNA 干扰应用的递送系统具有更大的潜力。 (C) 2012 Elsevier Inc. 保留所有权利。
Small interfering RNAs (siRNAs) are a potentially powerful new class of pharmaceutical drugs for many disease. However, the delivery of unprotected si RNAs is ineffective due to their susceptibility to degradation by ubiquitous nucleases under physiological conditions. Layered double hydroxide nanoparticles (LDHs) have been found to be efficient carriers of anionic drugs and nucleic acids. Our previous research has shown that LDHs (with the Z-average particle size of approximately 110 nm) can mediate siRNA delivery in mammalian cells, resulting in gene silencing. However, short double-stranded nucleic acids are mostly adsorbed onto the external surface and not well protected by LDHs. In order to enhance the intercalation of siRNA into the LDH interlayer and the efficiency of subsequent siRNA delivery, we prepared smaller LDHs (with the Z-average particle size of approximately 45 nm) with an engineered non-aqueous method. We demonstrate here that dsDNA/siRNA is more effectively intercalated into these small LDH nanoparticles, more dsDNA/siRNA is transfected into HEK 293T cells, and more efficient silencing of the target gene is achieved using smaller LDHs. Thus, smaller LDH particles have greater potential as a delivery system for the application of RNA interference. (C) 2012 Elsevier Inc. All rights reserved.