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Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2)

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Abstract

Background

An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2).

Methods and results

The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV–Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells.

Conclusions

The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.

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Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

AgNPs:

Silver nanoparticles

BSA:

Bovine serum albumin

EDC:

1-(3-Dimethyl aminopropyl)-3-ethylcarbodiimide hydrochloride

FT-IR:

Fourier transform infrared

PI:

Propidium iodide

UV–Vis:

Ultraviolet–visible

FESEM:

Field emission scanning electron microscopy

DLS:

Dynamic light scattering

PDI:

Polydispersity Index

PMA-DDA:

Poly (methacrylic acid-co-diallyl dimethyl ammonium chloride)

CSC:

Cancer stem cell

TFD:

Transcription factor decoy

ODN:

Oligodeoxynucleotide

DADMAC:

Diallyl dimethyl ammonium chloride

PBS:

Phosphate-buffered saline

DMSO:

Dimethyl sulfoxide

SEM:

Scanning electron microscopy

EDTA:

Ethylenediamine tetra-acetic acid

DEC:

Decoy

SCR:

Scramble

SiO2 :

Silicon dioxide

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Acknowledgements

The Medical Biotechnology Department staff of Zanjan University of Medical Sciences have been praised for their assistance by the authors.

Funding

The grant was received by Behrooz Johari from Zanjan University of Medical Sciences (Grant Number: A-12-1244-24 & Ethical Code: IR.ZUMS.BLC.1402.014).

Author information

Author notes

  1. Roghayeh Ghorbani and Behrooz Johari contributed equally to this work and hence are co-first authors.

Authors and Affiliations

  1. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Roghayeh Ghorbani & Behrooz Johari

  2. Student Research Committee, Zanjan University of Medical Sciences, Zanjan, Iran

    Roghayeh Ghorbani & Benyamin Keshavarz

  3. Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mahmoud Gharbavi

  4. Pain Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mahmoud Gharbavi

  5. Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Hamid Madanchi

  6. Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, 35131-38111, Iran

    Hamid Madanchi

  7. Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 13198, Iran

    Hamid Madanchi

  8. Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

    Behrooz Johari

Authors
  1. Roghayeh Ghorbani
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  2. Mahmoud Gharbavi
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  4. Hamid Madanchi
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Contributions

Roghayeh Ghorbani: Methodology, writing the original draft. Mahmoud Gharbavi: Methodology, review and editing. Benyamin Keshavarz: Methodology. Hamid Madanchi: Methodology, conceptualization, software, writing the original draft, and editing. Behrooz Johari: Supervision, project administration, conceptualization, writing the original draft, review, and editing, and final approval.

Corresponding authors

Correspondence to Hamid Madanchi or Behrooz Johari.

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All the authors declare no financial or commercial conflict of interest that could negatively influence the study.

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There was no human participant and consent was not required and no human or animal was involved in this study.

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Ghorbani, R., Gharbavi, M., Keshavarz, B. et al. Targeting c-Myc with decoy oligodeoxynucleotide-loaded polycationic nanoparticles inhibits cell growth and induces apoptosis in cancer stem-like cells (NTERA-2). Mol Biol Rep 51, 623 (2024). https://doi.org/10.1007/s11033-024-09559-6

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