Open AccessEffects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes
Author(s) -
Yoshiyuki Hattori,
Hiromu Saito,
Teruaki Oku,
Kei-ichi Ozaki
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12237
Subject(s) - cationic liposome , liposome , gene knockdown , transfection , gene silencing , microbiology and biotechnology , small interfering rna , biology , cationic polymerization , genetic enhancement , chemistry , biodistribution , biochemistry , in vitro , gene , organic chemistry
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), β‑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.