期刊
MOLECULAR MEDICINE REPORTS
卷 24, 期 2, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2021.12237
关键词
cationic liposome; sterol derivative; short interfering RNA delivery; lung; gene-knockdown
This study investigated the effects of sterol derivatives in systemically injected siRNA/cationic liposome complexes on gene-knockdown in the lungs of mice. The results showed that DDAB/Chol and DDAB/Ergo liposomes could function as vectors for siRNA delivery to the lungs, effectively increasing the suppression of Tie2 mRNA expression in mice.
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.
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