EF2-kinase targeted cobalt-ferrite siRNA-nanotherapy suppresses BRCA1-mutated breast cancer

Elif Asik, Yeliz Akpinar, Ayse Caner, Nermin Kahraman, Tulin Guray, Murvet Volkan, Constance Albarracin, Apar Pataer, Banu Arun, Bulent Ozpolat

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Aim: To investigate the role of EF2K in BRCA1-mutated breast cancer. Materials & methods: We developed silica coated cobalt-ferrite (CoFe) nanoparticles for in vivo delivery of small interfering RNAs (siRNAs) into BRCA1-mutated breast cancer. Results: Expression of EF2K is highly upregulated in the majority (78.5%) of BRCA1-mutated patients and significantly associated with poor patient survival and metastasis. Silencing of EF2K reduced cell proliferation, migration and invasion of the cancer cells. In vivo therapeutic targeting of EF2K by CoFe-siRNA-nanoparticles leads to sustained EF2K gene knockdown and suppressed tumor growth in orthotopic xenograft models of BRCA1-mutated breast cancer. Conclusion: EF2K is a potential novel molecular target in BRCA1-mutated tumors and CoFe-based siRNA nanotherapy may be used as a novel approach to target EF2K.

Original languageEnglish (US)
Pages (from-to)2315-2338
Number of pages24
JournalNanomedicine
Volume14
Issue number17
DOIs
StatePublished - 2019

Keywords

  • angiogenesis
  • BRCA1
  • breast cancer
  • EF2 kinase
  • gene-silencing therapy
  • invasion
  • metastasis
  • migration
  • nanoparticles
  • PARP inhibitor

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

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