Glypican-3 gene silencing for ovarian cancer using siRNA-PLGA hybrid micelles in a murine peritoneal dissemination model

Mai Hazekawa, Takuya Nishinakagawa, Tomoyo Kawakubo-Yasukochi, Manabu Nakashima

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Small interfering RNA (siRNA) has received much attention and for possible therapeutic applications to treat incurable chronic and genetic diseases, including cancer. However, the development of safe and efficient carriers for siRNA delivery still remains formidable hurdles for in vivo. The purpose of this study is to prepare siRNA–PLGA hybrid micelles to deliver the siRNA into the ovarian cancer cells and to evaluate of gene silencing effects in mice model. Here we focused on glypican-3 (Gpc3) gene silencing, which involved in tumor progression and inflammatory reaction, as a siRNA target in a murine ovarian cancer cells, HM-1. As a result, linear polyethyleneimine (LPEI)-coated siRNA–PLGA hybrid micelles were shown to effectively inhibit GPC3 expression in vitro in HM-1 cells, compared with siRNA in solution, because of their superior intracellular uptake and enhanced gene silencing effects. In addition, intraperitoneal administration of the cationic LPEI-coated siRNA–PLGA hybrid micelles decreased the number of tumor nodes in the mesentery, compared with the siRNA sole solution, in a HM-1 peritoneal dissemination model. These results suggested that siRNA–PLGA hybrid micelles could be an effective siRNA delivery tool in a murine ovarian cancer model, especially in case it targets molecules, such as Gpc3.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalJournal of Pharmacological Sciences
Volume139
Issue number3
DOIs
Publication statusPublished - Mar 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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