Comparative cellular pharmacokinetics and pharmacodynamics of siRNA delivery by SPANosomes and by cationic liposomes

被引：25

作者：

Zhou, Chenguang ^{[1
,2
]}

Zhang, Yue ^{[1
,3
]}

Yu, Bo ^{[2
,4
]}

Phelps, Mitch A. ^{[1
]}

Lee, L. James ^{[2
,4
]}

Lee, Robert J. ^{[1
,2
]}

机构：

[1] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA

[2] Ohio State Univ, NSF, Nanoscale Sci & Engn Ctr NSEC Affordable Nanoengn, Columbus, OH 43210 USA

[3] Chinese Acad Inspect & Quarantine, Inst Food Safety, Beijing, Peoples R China

[4] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2013年 / 9卷 / 04期

基金：

美国国家卫生研究院;

关键词：

RNA interference; siRNA; Nanoparticle; Cellular pharmacokinetics; Intracellular trafficking; LIPID-LIKE MATERIALS; INTRACELLULAR TRAFFICKING; RNAI THERAPEUTICS; IN-VITRO; GENE; CLATHRIN; KINETICS; CELLS; INTERNALIZATION; NANOPARTICLES;

D O I：

10.1016/j.nano.2012.10.002

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

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. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：504 / 513

页数：10

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