Optimization of Formulations Consisting of Layered Double Hydroxide Nanoparticles and Small Interfering RNA for Efficient Knockdown of the Target Gene,ACS Omega

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Optimization of Formulations Consisting of Layered Double Hydroxide Nanoparticles and Small Interfering RNA for Efficient Knockdown of the Target Gene
ACS Omega ( IF 3.7 ) Pub Date : 2018-05-02 00:00:00 , DOI: 10.1021/acsomega.8b00397
Yanheng Wu ₁ , Wenyi Gu ₁ , Chen Chen ₁ , Son Trong Do ₂ , Zhi Ping Xu ₁

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Layered double hydroxide (LDH) nanoparticles (NPs) are safe and effective vectors for small interfering RNA (siRNA) delivery. However, it is unclear whether there are optimal parameters for the efficient delivery of functional siRNA using LDH NPs. In this research, we comprehensively examined the effect of parameters, such as the mixing method and LDH/siRNA mass ratio on siRNA silencing capability. We first noted that the best way for loading gene segments (25 bp dsDNA and siRNA) is to add gene molecules to 100 nm LDH and then diluting in Dulbecco’s modified Eagle’s medium. Very interestingly, the optimal LDH/gene mass ratio is around 20:1 in terms of cellular uptake amount of gene segments, whereas this ratio is shifted to around 5:1 in terms of target gene silencing efficacy, which has been reasonably explained. The optimization for LDH NP-based gene delivery system may provide the guidance for more efficient in vitro and in vivo siRNA delivery using the optimal parameters.

中文翻译：

层状双氢氧化物纳米颗粒和小干扰RNA组成的制剂优化，用于有效敲低靶基因

层状双氢氧化物 (LDH) 纳米颗粒 (NP) 是安全有效的小干扰 RNA (siRNA) 递送载体。然而，尚不清楚是否存在使用 LDH NP 有效递送功能性 siRNA 的最佳参数。在本研究中，我们综合考察了混合方法、LDH/siRNA质量比等参数对siRNA沉默能力的影响。我们首先注意到，加载基因片段（25 bp dsDNA 和 siRNA）的最佳方法是将基因分子添加到 100 nm LDH 中，然后在 Dulbecco 改良的 Eagle 培养基中稀释。非常有趣的是，就基因片段的细胞摄取量而言，最佳的LDH/基因质量比约为20：1，而就靶基因沉默功效而言，该比例转移至5：1左右，这已经得到了合理的解释。基于 LDH NP 的基因递送系统的优化可以为使用最佳参数更有效的体外和体内 siRNA 递送提供指导。

更新日期：2018-05-02

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