PMID- 34165169
OWN - NLM
STAT- MEDLINE
DCOM- 20211117
LR  - 20211117
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 24
IP  - 2
DP  - 2021 Aug
TI  - Effects of sterol derivatives in cationic liposomes on biodistribution and 
      gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes.
LID - 598 [pii]
LID - 10.3892/mmr.2021.12237 [doi]
AB  - Cationic liposomes can be intravenously injected to deliver short interfering 
      (si)RNAs into the lungs. The present study investigated the effects of sterol 
      derivatives in systemically injected siRNA/cationic liposome complexes (siRNA 
      lipoplexes) on gene‑knockdown in the lungs of mice. Cationic liposomes composed 
      of 1,2‑dioleoyl‑3‑trimethylammonium‑propane or dimethyldioctadecylammonium 
      bromide (DDAB) were prepared as a cationic lipid, with sterol derivatives such as 
      cholesterol (Chol), beta‑sitosterol, ergosterol (Ergo) or stigmasterol as a neutral 
      helper lipid. Transfected liposomal formulations composed of DDAB/Chol or 
      DDAB/Ergo did not suppress the expression of the luciferase gene in LLC‑Luc and 
      Colon 26‑Luc cells in vitro, whereas other formulations induced moderate 
      gene‑silencing. The systemic injection of siRNA lipoplexes formulated with Chol 
      or Ergo into mice resulted in abundant siRNA accumulation in the lungs. In 
      comparison, systemically injected DDAB/Chol or DDAB/Ergo lipoplexes of Tie2 siRNA 
      effectively increased the suppression of the Tie2 mRNA expression in the lungs of 
      mice. These findings indicated that DDAB/Chol and DDAB/Ergo liposomes could 
      function as vectors for siRNA delivery to the lungs.
FAU - Hattori, Yoshiyuki
AU  - Hattori Y
AD  - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan.
FAU - Saito, Hiromu
AU  - Saito H
AD  - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan.
FAU - Oku, Teruaki
AU  - Oku T
AD  - Department of Microbiology, Hoshi University, Tokyo 142-8501, Japan.
FAU - Ozaki, Kei-Ichi
AU  - Ozaki KI
AD  - Department of Molecular Pathology, Faculty of Pharmaceutical Sciences, Doshisha 
      Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
LA  - eng
PT  - Journal Article
DEP - 20210624
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Cations)
RN  - 0 (Liposomes)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sterols)
RN  - 251IW5I21C (dimethyldioctadecylammonium)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Cations/*pharmacology
MH  - Cell Line, Tumor
MH  - Cholesterol/analogs & derivatives
MH  - Drug Delivery Systems
MH  - Female
MH  - Gene Knockdown Techniques/*methods
MH  - Gene Silencing
MH  - Liposomes/*pharmacology
MH  - *Lung
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Quaternary Ammonium Compounds
MH  - RNA, Small Interfering/*administration & dosage
MH  - Sterols/*chemistry/*pharmacology
MH  - Tissue Distribution/*drug effects
MH  - Transfection
PMC - PMC8240178
OTO - NOTNLM
OT  - cationic liposome
OT  - gene-knockdown
OT  - lung
OT  - short interfering RNA delivery
OT  - sterol derivative
COIS- The authors declare that they have no competing interests.
EDAT- 2021/06/25 06:00
MHDA- 2021/11/18 06:00
PMCR- 2021/06/23
CRDT- 2021/06/24 09:35
PHST- 2021/03/25 00:00 [received]
PHST- 2021/06/04 00:00 [accepted]
PHST- 2021/06/24 09:35 [entrez]
PHST- 2021/06/25 06:00 [pubmed]
PHST- 2021/11/18 06:00 [medline]
PHST- 2021/06/23 00:00 [pmc-release]
AID - 598 [pii]
AID - MMR-0-0-12237 [pii]
AID - 10.3892/mmr.2021.12237 [doi]
PST - ppublish
SO  - Mol Med Rep. 2021 Aug;24(2):598. doi: 10.3892/mmr.2021.12237. Epub 2021 Jun 24.