Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model

Thais Leite Nascimento, Hervé Hillaireau, Juliette Vergnaud, Melania Rivano, Claudine Deloménie, Delphine Courilleau, Silvia Arpicco, Jung Soo Suk, Justin S Hanes, Elias Fattal

Research output: Contribution to journalArticle

Abstract

We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.

Original languageEnglish (US)
Pages (from-to)103-111
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume514
Issue number1
DOIs
StatePublished - Nov 30 2016

Keywords

  • A549
  • CD44
  • Hyaluronic acid
  • Lipoplexes
  • Luciferase
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Leite Nascimento, T., Hillaireau, H., Vergnaud, J., Rivano, M., Deloménie, C., Courilleau, D., Arpicco, S., Suk, J. S., Hanes, J. S., & Fattal, E. (2016). Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model. International Journal of Pharmaceutics, 514(1), 103-111. https://doi.org/10.1016/j.ijpharm.2016.06.125