The efficiency of lipid nanoparticles with an original cationic lipid as a siRNA delivery system for macrophages and dendritic cells

Small interfering of RNA (siRNA) technology has the potential to be a next-generation therapy. However, naked siRNA does not have high transfection efficiency and is rapidly degraded after systemic injection, so an appropriate drug delivery system (DDS) is required for clinical use. Several potentia...

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Bibliographic Details
Published in:Pharmaceutical development and technology 2019-03, Vol.24 (3), p.263-268
Main Authors: Uemura, Yasunori, Naoi, Tomoyuki, Kanai, Yasumasa, Kobayashi, Katsuya
Format: Article
Language:English
Subjects:
dendritic cells
Lipid nanoparticles
macrophages
small interfering RNA
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Summary:Small interfering of RNA (siRNA) technology has the potential to be a next-generation therapy. However, naked siRNA does not have high transfection efficiency and is rapidly degraded after systemic injection, so an appropriate drug delivery system (DDS) is required for clinical use. Several potential systems have been assessed, clinically focusing on hepatocyte or cancer tissue using siRNA. However, targeting immune cells using siRNA is still challenging, and a new DDS is required. In this study, we prepared lipid nanoparticles (LNP) composed of original cationic lipid, neutral lipid of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and PEG2000-DMPE (N-(carbonyl-methoxypolyethyleneglycol 2000)-1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, sodium salt). Our LNP encapsulating siRNA (LNP/siRNA) exerted a knock-down (KD) effect on mouse inflammatory peritoneal macrophages in vitro. In addition, an in vivo KD effect by systemic administration of LNP/siRNA was observed in macrophages and dendritic cells (DCs) in mice. Furthermore, our LNP/siRNA showed in vitro KD effects not only on murine cells but also on human cells like monocyte-derived macrophages (MDMs) and monocyte-derived DCs (MDDCs). These results indicate the potential utility of our LNP for siRNA-based therapy targeting macrophages and DCs. Because these cells are known to have a significant role in several kinds of diseases, and siRNA can specifically suppress target genes that are closely associated with disease states and are untreatable by small molecules or antibodies. Therefore, delivering siRNA by our LNP to macrophages and DCs could provide novel therapies.
ISSN:1083-7450
1097-9867
DOI:10.1080/10837450.2018.1469149