Effects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes.
Mol Med Rep
; 24(2)2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34165169
ABSTRACT
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 geneknockdown in the lungs of mice. Cationic liposomes composed of 1,2dioleoyl3trimethylammoniumpropane or dimethyldioctadecylammonium bromide (DDAB) were prepared as a cationic lipid, with sterol derivatives such as cholesterol (Chol), ßsitosterol, 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 LLCLuc and Colon 26Luc cells in vitro, whereas other formulations induced moderate genesilencing. 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sterols
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Tissue Distribution
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Cations
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RNA, Small Interfering
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Gene Knockdown Techniques
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Liposomes
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Lung
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2021
Document type:
Article
Affiliation country: