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

Author:

Asik Elif12,Akpinar Yeliz34,Caner Ayse1,Kahraman Nermin1,Guray Tulin2,Volkan Murvet3,Albarracin Constance5,Pataer Apar6,Arun Banu7,Ozpolat Bulent18

Affiliation:

1. Department of Experimental Therapeutics, The University of Texas-MD Anderson Cancer Center, Houston, TX 77054, USA

2. Department of Biotechnology, Middle East Technical University, Ankara 06800, Turkey

3. Department of Chemistry, Middle East Technical University, Ankara 06800, Turkey

4. Department of Chemistry, Kırsehir Ahi Evran University, Kırsehir 40100, Turkey

5. Department of Pathology, Division of Pathology/Lab Medicine, MD Anderson Cancer Center, Houston, TX 77054, USA

6. Department of Thoracic Surgery, MD Anderson Cancer Center, Houston, TX 77054, USA

7. Departments of Breast Medical Oncology & Breast Cancer Genetics, The University of Texas-MD Anderson Cancer Center, Houston, TX 77054, USA

8. Center for RNA Interference & Non-Coding RNA, The University of Texas-MD Anderson Cancer Center, Houston, TX 77054, USA

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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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