Delivery of siRNA Using Lipid Nanoparticles Modified with Cell Penetrating Peptide

Yuhuan Li, Robert J. Lee, Kongtong Yu, Ye Bi, Yuhang Qi, Yating Sun, Yujing Li, Jing Xie, Lesheng Teng

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51 Citations (Scopus)


Clinical development of siRNA has been hindered by the lack of an effective delivery system. Here, we report the construction of a novel siRNA delivery system, sTOLP, which is based on cell penetrating peptide oleoyl-octaarginine (OA-R8) modified multifunctional lipid nanoparticles. sTOLP nanoparticles are composed of a protamine complexed siRNA core, OA-R8, cationic and PEGylated lipids, and transferrin as a targeting ligand. sTOLP formulation was optimized and characterized in vitro and showed excellent gene silencing activity. In vivo, siRNA encapsulated in sTOLP exhibited potent tumor inhibition (61.7%) and was preferentially taken up by hepatocytes and tumor cells in HepG2-bearing nude mice without inducing immunogenicity or hepatic or renal toxicity. Furthermore, sTOLP-loaded siRNA had stability in circulation greater than that of free siRNA. These data demonstrated potential utility of sTOLP-mediated siRNA delivery in cancer therapy.

Original languageEnglish
Pages (from-to)26613–26621
Number of pages9
JournalACS Applied Materials & Interfaces
Issue number40
Publication statusPublished - 12 Oct 2016
Externally publishedYes


  • cancer
  • cell penetrating peptide
  • drug delivery
  • lipid nanoparticles
  • multifunctional
  • siRNA

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