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

Asik E., Akpinar Y., Caner A., Kahraman N., GÜRAY N. T., Volkan M., ...More

NANOMEDICINE, vol.14, no.17, pp.2315-2338, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 17
  • Publication Date: 2019
  • Doi Number: 10.2217/nnm-2019-0132
  • Journal Name: NANOMEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2315-2338
  • Keywords: angiogenesis, BRCA1, breast cancer, EF2 kinase, gene-silencing therapy, invasion, metastasis, migration, nanoparticles, PARP inhibitor, FACTOR 2 KINASE, RIBOSE POLYMERASE INHIBITORS, POLY(ADP-RIBOSE) POLYMERASE, ELONGATION-FACTOR-2 KINASE, MAGNETIC NANOPARTICLES, TUMOR-SUPPRESSOR, STEM-CELLS, BRCA1, ANGIOGENESIS, SRC
  • Middle East Technical University Affiliated: Yes

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 themajority (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.