Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer

SHAHBAZI R., ASİK E., KAHRAMAN N., Turk M., OZPOLAT B., ULUBAYRAM K.

NANOMEDICINE, cilt.12, sa.16, ss.1961-1973, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 12 Sayı: 16
  • Basım Tarihi: 2017
  • Doi Numarası: 10.2217/nnm-2017-0081
  • Dergi Adı: NANOMEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1961-1973
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.