Evaluation of combined effect of hyperthermia and ionizing radiation on cytotoxic damages induced by IUdR-loaded PCL-PEG-coated magnetic nanoparticles in spheroid culture of U87MG glioblastoma cell line

Abstract

Purpose: Glioblastoma multiform (GBM) is the most prevalent and aggressive type of primary brain tumor. None of the current conventional treatment methods has improved treatment considerably. Therefore, in this study the effect of magnetic nanoparticles coated with poly (caprolactone)-poly (ethylene glycol) (PCL-PEG) as a 5-iodo 2′deoxyuridine (IUdR) carrier in the presence of hyperthermia and 6 MV (megavoltage) X-ray radiation, were investigated in a spheroid model of U87MG glioblastoma cell line using colony formation assay.

Materials and methods: First, the human glioblastoma cell line U87MG was cultured as a spheroid using the liquid overlay technique. Spheroids on day 10 with 100 mm diameters were treated with 1 µM IUdR or nanoparticles as IUdR carriers for one volume doubling time (VDT) of spheroids (67 h) and hyperthermia at 43 °C for 1 h, and then irradiated with 2 Gy of 6 MV X-ray in different groups. Finally, the effect of treatment on colony-forming ability was obtained by colony formation and alkaline assay.

Results: Our results revealed that hyperthermia in combination with radiation could significantly reduce the colony number of glioblastoma spheroid cells treated with IUdR or nanoparticles as IUdR carriers. However, the extent of reduction in colony number following treatment with IUdR-loaded nanoparticles in combination with hyperthermia and then X-ray radiation was significantly more than free IUdR.

Conclusion: According to this study, PCL-PEG-coated magnetic nanoparticles are effective delivery vehicles for IUdR into cells. Moreover, they can act as a radiosensitizer and thermosensitizer in the treatment of the glioblastoma cell line.

Keywords:

• PEG-PCL
• iododeoxyuridine
• ionizing radiation
• hyperthermia
• spheroid

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by grants No. 93038401 from Iran National Science Foundation (INSF).

Notes on contributors

Parisa Rezaie

Parisa Rezaie received her Associate Degree in Radiology from the University of Hamedan, Hamedan, in 2008. She then continued to accomplish her B.S. degree in Radiology from University of Tehran, Tehran, in 2012 and her M.S. degree in Medical Physics from Iran University of Medical Sciences, Tehran, in 2017. Her research interests are in nanobiotechnology and radiation. She is currently working in the Radiotherapy Center of Laleh Hospital in Tehran.

Samideh Khoei

Samideh Khoei received her PhD degree in Biophysics from the University of Tehran, Tehran, Iran, in 2004. She worked at the Iran University of Medical Sciences (IUMS) as assistant professor (2005–2012) and continued as associate professor (2012–2016). Since 2016, she continued her work as professor at IUMS. She is head of the Medical Physics department. She is lecturer of Radiobiology and Ionizing Radiation Protection. She is a reviewer of several international and national journals. She is author/coauthor of more than 50 scientific papers in international journals. Her research interests are the study of the cytotoxic and genotoxic effects of nanoparticles as carrier of anti-cancer drugs in combination with radiotherapy or hyperthermia.

Sepideh Khoee

Sepideh Khoee received her PhD in Polymer Chemistry in 2002 at Isfahan University of Technology, Isfahan, Iran. She joined the Chemistry Faculty at the University of Tehran (UT) in 2003 as an assistant professor. She continued her career as an associate professor in 2008 and was appointed as a full professor of Polymer Chemistry at the University of Tehran in 2014. She is the recipient of several awards, including the selected executive director of applied research in the 22nd Research Festival of UT (2013) and the outstanding researcher in the 7th Iran Nano Festival by Iran Nanotechnology Initiative Council (INIC), 2013. Her research interests include design and synthesis of polymeric biomaterials, hybrid nanoparticles, medicinal chemistry and drug delivery systems.

Sakine Shirvalilou

Sakine Shirvalilou received her B.S. degree in Physics from Tabriz University, Tabriz, in 2005 and her M.S. degree in Atomic and molecular Physics from Azad University of Mahabad, Mahabad, in 2011. She is currently working on her Ph.D. thesis in Medical Physics at Iran University of Medical Sciences (IUMS), Tehran. Her research interests are in nanobiomaterials, radiobiology and hyperthermia. She is currently working on glioblastoma and testing novel RF hyperthermia-based therapy on rat brains.

Seied Rabi Mahdavi

Seied Rabi Mahdavi received his PhD in Medical Physics at Tehran University of Medical Sciences, Tehran, Iran, in 2004. He has taken a complementary course of European Radiation Biology at Gray Lab-Mount Vernon Hospital in London. He is associate professor of Medical Physics at Iran University of Medical Sciences and lecturer of Radiotherapy Physics and Dosimetry. He is Radiotherapy Physicist. He has more than 110 scientific papers in international and national journals. He is President of Iranian Association of Medical Physics (IAMP) and Vice-president of Middle East Federation of Organization of Medical Physics (MEFOMP). His research interests are Radiotherapy Physics, treatment planning and clinical radiobiology.