RRC ID 59682
Author Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M.
Title Glypican-3 gene silencing for ovarian cancer using siRNA-PLGA hybrid micelles in a murine peritoneal dissemination model.
Journal J Pharmacol Sci
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.
Volume 139(3)
Pages 231-239
Published 2019-3-1
DOI 10.1016/j.jphs.2019.01.009
PII S1347-8613(19)30014-3
PMID 30803892
MeSH Animals Female Gene Silencing Glypicans / genetics* Mice Micelles Ovarian Neoplasms / genetics Ovarian Neoplasms / therapy* Peritoneal Neoplasms / genetics Peritoneal Neoplasms / secondary Peritoneal Neoplasms / therapy Polylactic Acid-Polyglycolic Acid Copolymer / chemistry* RNA, Small Interfering / administration & dosage*
IF 2.835
Times Cited 3
Human and Animal Cells OV2944-HM-1(RCB1483)