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Enhancement of Radio-Thermo-Sensitivity of 5-Iodo-2-Deoxyuridine-Loaded Polymeric-Coated Magnetic Nanoparticles Triggers Apoptosis in U87MG Human Glioblastoma Cancer Cell Line

Cellular and Molecular Bioengineering volume 14, pages 365–377 (2021)Cite this article

Abstract

Introduction

With an emphasis on the radioresistant nature of glioblastoma cells, the aim of the present study was to evaluate the radio-thermo-sensitizing effects of PCL-PEG-coated Superparamagnetic iron oxide nanoparticles (SPIONs) as a carrier of 5-iodo-2-deoxyuridine (IUdR) in monolayer culture of U87MG human glioma cell line.

Methods

Following monolayer culture of U87MG cells, nanoparticle uptake was assessed using Prussian blue staining and ICP-OES method. The U87MG cells were treated with an appropriate concentration of free IUdR and PCL-PEG-coated SPIONs (MNPs) loaded with IUdR (IUdR/MNPs) for 24 h, subjected to hyperthermia (water bath and alternating magnetic field (AMF)) at 43 °C, and exposed to X-ray (2 Gy, 6 MV). The combined effects of hyperthermia with or without magnetic nanoparticles on radiosensitivity of the U87MG cells were evaluated using colony formation assay (CFA) and Flowcytometry.

Results

Prussian blue staining and ICP-OES showed that the nanoparticles were able to enter the cells. The results also indicated that IUdR/MNPs combined with X-ray radiation and hyperthermia significantly decreased the colony formation ability of monolayer cells (1.11, 1.41 fold) and increased the percentage of apoptotic (2.47, 4.1 fold) and necrotic cells (12.28, 29.34 fold), when compared to IUdR combined with X-ray and hyperthermia or IUdR/MNPs + X-ray. MTT results revealed that the presence of IUdR/MNPs significantly increased the toxicity of AMF hyperthermia compared to the water bath method.

Conclusions

Our study showed that SPIONs/PCL-PEG, as a carrier of IUdR, can enhance the cytotoxic effects of radiotherapy and hyperthermia and act as a radio-thermo-sensitizing agent.

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Acknowledgments

We thank Pasteur Institute of Iran for providing U87MG cells. The Radiotherapy Centre of Asia Hospital is acknowledged for providing training and equipment for Radiotherapy.

Conflict of interest

The author(s) declared no conflict of interest.

Ethical Approval

No human studies were carried out by the author for this article. No animal studies were carried out by the authors for this article.

Funding

This work was supported by Grant No. 25052 from the School of Medicine of Iran University of Medical Sciences (IUMS).

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Authors and Affiliations

  1. Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

    Samideh Khoei & Sakine Shirvalilou

  2. Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran

    Samideh Khoei, Sakine Shirvalilou & Seied Rabi Mahdavi

  3. Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Vahid Hosseini & Jalil Pirayesh Islamian

  4. Department of Polymer Chemistry, School of Chemistry, College of Science, University of Tehran, Tehran, Iran

    Mehdi Hosseini & Sepideh Khoee

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  1. Samideh Khoei
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  2. Vahid Hosseini
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  3. Mehdi Hosseini
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  4. Sepideh Khoee
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Correspondence to Samideh Khoei or Sakine Shirvalilou.

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Khoei, S., Hosseini, V., Hosseini, M. et al. Enhancement of Radio-Thermo-Sensitivity of 5-Iodo-2-Deoxyuridine-Loaded Polymeric-Coated Magnetic Nanoparticles Triggers Apoptosis in U87MG Human Glioblastoma Cancer Cell Line. Cel. Mol. Bioeng. 14, 365–377 (2021). https://doi.org/10.1007/s12195-021-00675-y

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Keywords

  • 5-iodo-2-deoxyuridine
  • Glioblastoma
  • Water bath hyperthermia
  • Alternating magnetic field
  • Ionizing radiation
  • Apoptosis