Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.

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Unal O., Akkoc Y., Kocak M., Nalbat E., Dogan-Ekici A., Yagci A., ...Daha Fazla

Journal of nanobiotechnology, cilt.18, ss.65, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1186/s12951-020-00615-4
  • Dergi Adı: Journal of nanobiotechnology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Compendex, EMBASE, INSPEC, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.65
  • Anahtar Kelimeler: SPION, Theranostic nanoparticle, Cancer treatment, Gene therapy, MicroRNA, MIR376B, Autophagy, GENE DELIVERY, THERAPY, ARGONAUTE2, EXPRESSION, RESISTANCE, CISPLATIN, VECTORS, SYSTEMS
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fuorophoretagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer.