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Article Open Access

Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice

  • Authors:
    • Yoshiyuki Hattori
    • Kyoko Tamaki
    • Sho Sakasai
    • Kei‑Ichi Ozaki
    • Hiraku Onishi
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142‑8501, Japan, Department of Drug Delivery Research, Hoshi University, Tokyo 142‑8501, Japan, Department of Molecular Pathology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610‑0395, Japan
    Copyright: © Hattori et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4183-4196
    |
    Published online on: September 18, 2020
       https://doi.org/10.3892/mmr.2020.11525
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Abstract

Polyethylene glycol (PEG)‑modifications (PEGylations) of cationic liposome/small interfering RNA complexes (siRNA lipoplexes) can enhance their systemic stability. The present study determined the effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution after intravenous injection. Three types of dialkyl or trialkyl cationic lipids were used in the current study for the preparation of cationic liposomes. Additionally, various PEGylated siRNA lipoplexes that contained PEG‑1,2‑distearoyl‑sn‑­glycero‑­3‑phosphoethanolamine (DSPE), PEG‑1,2‑distearoyl‑rac‑glycero‑3‑­methylpolyoxyethylene (DSG), PEG‑cholesterol (PEG‑Chol) and PEG‑chondroitin sulfate conjugate (PEG‑CS) were prepared. The results revealed that PEGylation of siRNA lipoplexes with PEG‑DSPE strongly decreased gene‑silencing effects in cells. In contrast, those with PEG‑DSG, PEG‑Chol and PEG‑CS did not largely decrease gene-silencing effects. However, regardless of the PEG‑derivative type, PEGylation of siRNA lipoplexes decreased their agglutination with erythrocytes. Furthermore, intravenous injection of PEGylated siRNA lipoplexes markedly decreased the accumulation of siRNA in the lungs, regardless of the type of PEG‑derivative. However, non‑PEGylated siRNA lipoplexes accumulated mainly in the lungs regardless of the siRNA lipoplex cationic lipid type. The results indicated that PEGylation of siRNA lipoplexes with PEG‑DSG, PEG‑Chol and PEG‑CS may improve systemic stability without losing transfection activity by PEGylation.
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Copy and paste a formatted citation
Spandidos Publications style
Hattori Y, Tamaki K, Sakasai S, Ozaki KI and Onishi H: Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice. Mol Med Rep 22: 4183-4196, 2020.
APA
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., & Onishi, H. (2020). Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice. Molecular Medicine Reports, 22, 4183-4196. https://doi.org/10.3892/mmr.2020.11525
MLA
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., Onishi, H."Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice". Molecular Medicine Reports 22.5 (2020): 4183-4196.
Chicago
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., Onishi, H."Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice". Molecular Medicine Reports 22, no. 5 (2020): 4183-4196. https://doi.org/10.3892/mmr.2020.11525
Copy and paste a formatted citation
x
Spandidos Publications style
Hattori Y, Tamaki K, Sakasai S, Ozaki KI and Onishi H: Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice. Mol Med Rep 22: 4183-4196, 2020.
APA
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., & Onishi, H. (2020). Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice. Molecular Medicine Reports, 22, 4183-4196. https://doi.org/10.3892/mmr.2020.11525
MLA
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., Onishi, H."Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice". Molecular Medicine Reports 22.5 (2020): 4183-4196.
Chicago
Hattori, Y., Tamaki, K., Sakasai, S., Ozaki, K., Onishi, H."Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice". Molecular Medicine Reports 22, no. 5 (2020): 4183-4196. https://doi.org/10.3892/mmr.2020.11525
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