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Influence of cationic lipid composition on uptake and intracellular processing of lipid nanoparticle formulations of siRNA
- Source :
- Nanomedicine: Nanotechnology, Biology and Medicine. 9:233-246
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The in vivo gene silencing potencies of lipid nanoparticle (LNP)-siRNA systems containing the ionizable cationic lipids DLinDAP, DLinDMA, DLinKDMA, or DLinKC2-DMA can differ by three orders of magnitude. In this study, we examine the uptake and intracellular processing of LNP-siRNA systems containing these cationic lipids in a macrophage cell-line in an attempt to understand the reasons for different potencies. Although uptake of LNP is not dramatically influenced by cationic lipid composition, subsequent processing events can be strongly dependent on cationic lipid species. In particular, the low potency of LNP containing DLinDAP can be attributed to hydrolysis by endogenous lipases following uptake. LNP containing DLinKC2-DMA, DLinKDMA, or DLinDMA, which lack ester linkages, are not vulnerable to lipase digestion and facilitate much more potent gene silencing. The superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to higher uptake and improved ability to stimulate siRNA release from endosomes subsequent to uptake.This study reports on the in vivo gene silencing potency of lipid nanoparticle-siRNA systems containing ionizable cationic lipids. It is concluded that the superior potency of DLinKC2-DMA compared with DLinKDMA or DLinDMA can be attributed to their higher uptake thus improved ability to stimulate siRNA release from endosome.
- Subjects :
- Endosome
Biomedical Engineering
Pharmaceutical Science
Medicine (miscellaneous)
Bioengineering
Endocytosis
Cell Line
Mice
Ribonucleases
In vivo
Cations
Animals
Gene silencing
General Materials Science
RNA, Small Interfering
Lipase
biology
Chemistry
Macrophages
Cationic polymerization
Lipid metabolism
Lipid Metabolism
Lipids
Clathrin
Biochemistry
biology.protein
Nanoparticles
Pinocytosis
Molecular Medicine
RNA Interference
Intracellular
Subjects
Details
- ISSN :
- 15499634
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Nanomedicine: Nanotechnology, Biology and Medicine
- Accession number :
- edsair.doi.dedup.....efd322577cf6276546a23249c62a2780