Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes.
Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes.
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DOI：
10.1016/j.nano.2012.10.002
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发表时间：
2013-05
影响因子：
5.4
通讯作者：
Lee, Robert J.
中科院分区：
文献类型：
--
作者：
Zhou, Chenguang;Zhang, Yue;Yu, Bo;Phelps, Mitch A.;Lee, L. James;Lee, Robert J.
了解细胞内运输的机制对于小干扰RNA（siRNA）递送载体的开发是重要的。在这里，我们描述了一种新的方法来定量分析纳米载体介导的siRNA的处置。通过使用流式细胞术测量荧光标记的siRNA和分子信标的荧光强度来定量siRNA随时间的细胞摄取和细胞质释放。该方法用于研究通过SPANosomes（SP）和通过阳离子脂质体（CL）递送siRNA的细胞药代动力学（PK）。结果表明，SP的上级药效学（PD）响应是因为与CL相比，其增强了siRNA向细胞质中的转运。两种制剂的不同细胞药代动力学特征与不同的细胞进入途径相关。这些发现可以促进未来更有效的siRNA递送载体的合理设计。
Mechanistic understanding of intracellular trafficking is important for the development of small interfering RNA (siRNA) delivery vehicles. Here, we describe a novel methodology to quantitatively analyze nanocarrier-mediated disposition of siRNA. Cellular uptake and cytoplasmic release of siRNA over time were quantified by measuring the fluorescence intensities of fluorescently-labeled siRNAs and molecular beacons using flow cytometry. This method was used to investigate the cellular pharmacokinetics (PK) of siRNA delivery by SPANosomes (SP) and by cationic liposomes (CL). The results showed that the superior pharmacodynamic (PD) response of SP was because it enhanced transport of siRNA into the cytoplasm compared to the CL. The divergent cellular pharmacokinetic profiles of the two formulations were associated with different cellular entry pathways. These findings can facilitate the rational design of more efficient siRNA delivery vehicles in the future.
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