Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

Roghayeh Ghorbani; Mahmoud Gharbavi; Ali Sharafi; Elham Rismani; Hamed Rezaeejam; Yousef Mortazavi; Behrooz Johari

doi:10.32604/or.2023.044741

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

Oncol Res. 2023 Nov 15;32(1):101-125. doi: 10.32604/or.2023.044741. eCollection 2023.

Authors

Roghayeh Ghorbani¹, Mahmoud Gharbavi², Ali Sharafi^{3

4}, Elham Rismani⁵, Hamed Rezaeejam⁶, Yousef Mortazavi¹, Behrooz Johari³

Affiliations

¹ Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
² Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
⁴ Department of Pharmaceutical Biotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
⁵ Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Iran.
⁶ Department of Radiology Technology, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Abstract

In the present study, we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells. Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays. ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure. The physicochemical characteristics of nanostructures were determined by FTIR, DLS, UV-vis, TEM, EDX, in vitro release, and hemolysis tests. Subsequently, the cytotoxicity properties of them with and without X-irradiation were investigated by uptake, MTT, cell cycle, apoptosis, and scratch assays on the LNCaP cell line. The results of DLS and TEM showed negative charge (-9 mV) and nanometer size (40 nm) for Se@BSA@Chi-DEC-MTX NPs, respectively. The results of FTIR, UV-vis, and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles. The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL. The ODNs release from the nanostructures showed a pH-dependent manner, and the release rate was 15% higher in acidic pH. The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen (PSMA). The significant synergistic effects of nanostructure (containing MTX drug) treatment along with X-irradiation showed cell growth inhibition, apoptosis induction (~57%), cell cycle arrest (G2/M phase), and migration inhibition (up to 90%) compared to the control. The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells. This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Keywords: Chemoradiotherapy; Combination therapy; Decoy oligodeoxynucleotides; Myc transcription factor; Prostate cancer; Selenium nanoparticle.

MeSH terms

Chemoradiotherapy
Hemolysis
Humans
Male
Molecular Docking Simulation
Nanostructures*
Prostate
Prostatic Neoplasms* / drug therapy
Selenium* / pharmacology

Substances

Selenium