PMID- 29688101
OWN - NLM
STAT- MEDLINE
DCOM- 20190307
LR  - 20190307
IS  - 1097-9867 (Electronic)
IS  - 1083-7450 (Linking)
VI  - 24
IP  - 3
DP  - 2019 Mar
TI  - The efficiency of lipid nanoparticles with an original cationic lipid as a siRNA 
      delivery system for macrophages and dendritic cells.
PG  - 263-268
LID - 10.1080/10837450.2018.1469149 [doi]
AB  - 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.
FAU - Uemura, Yasunori
AU  - Uemura Y
AD  - a R&D Division , Kyowa Hakko Kirin Co., Ltd , Nagaizumi-cho, Sunto-gun , Japan.
FAU - Naoi, Tomoyuki
AU  - Naoi T
AD  - b R&D Division , Kyowa Hakko Kirin Co., Ltd , Machida , Japan.
FAU - Kanai, Yasumasa
AU  - Kanai Y
AD  - a R&D Division , Kyowa Hakko Kirin Co., Ltd , Nagaizumi-cho, Sunto-gun , Japan.
FAU - Kobayashi, Katsuya
AU  - Kobayashi K
AD  - a R&D Division , Kyowa Hakko Kirin Co., Ltd , Nagaizumi-cho, Sunto-gun , Japan.
LA  - eng
PT  - Journal Article
DEP - 20180508
PL  - England
TA  - Pharm Dev Technol
JT  - Pharmaceutical development and technology
JID - 9610932
RN  - 0 (Cations)
RN  - 0 (Lipids)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Cations
MH  - Dendritic Cells/metabolism
MH  - Gene Knockdown Techniques
MH  - *Gene Transfer Techniques
MH  - Humans
MH  - Lipids/*chemistry
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - *Nanoparticles
MH  - RNA, Small Interfering/*administration & dosage
MH  - Transfection
OTO - NOTNLM
OT  - Lipid nanoparticles
OT  - dendritic cells
OT  - macrophages
OT  - small interfering RNA
EDAT- 2018/04/25 06:00
MHDA- 2019/03/08 06:00
CRDT- 2018/04/25 06:00
PHST- 2018/04/25 06:00 [pubmed]
PHST- 2019/03/08 06:00 [medline]
PHST- 2018/04/25 06:00 [entrez]
AID - 10.1080/10837450.2018.1469149 [doi]
PST - ppublish
SO  - Pharm Dev Technol. 2019 Mar;24(3):263-268. doi: 10.1080/10837450.2018.1469149. 
      Epub 2018 May 8.