Effect of radiation energy and intracellular iron dose on iron oxide nanoparticle enhancement of radiation cytotoxicity

Courtney M. Mazur, Rendall R. Strawbridge, Ella S. Thompson, Alicia A. Petryk, David J. Gladstone, P. Jack Hoopes

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Iron oxide nanoparticles (IONPs) are one of several high-Z materials currently being investigated for their ability to enhance the cytotoxic effects of therapeutic ionizing radiation. Studies with iron oxide, silver, gold, and hafnium oxide suggest radiation dose, radiation energy, cell type, and the type and level of metallic nanoparticle are all critical factors in achieving radiation enhancement in tumor cells. Using a single 4 Gy radiation dose, we compared the level of tumor cell cytotoxicity at two different intracellular iron concentrations and two different radiation energies in vitro. IONPs were added to cell culture media at concentrations of 0.25 mg Fe/mL and 1.0 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for 72 hours. Extracellular iron was then removed and cells were irradiated at either 662 keV or 10 MV. At the 0.25 mg Fe/mL dose (4 pg Fe/cell), radiation energy did not affect the level of cytotoxicity. However with 1.0 mg Fe/mL (9 pg Fe/cell), the higher 10 MV radiation energy resulted in 50% greater cytotoxicity as compared to cells without IONPs irradiated at this energy. These results suggest IONPs may be able to significantly enhance the cytotoxic effects of radiation and improve therapeutic ratio if they can be selectively associated with cancer cells and/or tumors. Ongoing in vivo studies of IONP radiation enhancement in a murine tumor model are too immature to draw conclusions from at this time, however preliminary data suggests similar effectiveness of IONP radiation enhancement at 6 MV and 18 MV energy levels. In addition to the IONP-based radiation enhancement demonstrated here, the use of tumor-localized IONP with an externally delivered, non-toxic alternating magnetic field affords the opportunity to selectively heat and kill tumor cells. Combining IONP-based radiation sensitization and heat-based cytotoxicity provides a unique and potentially highly effective opportunity for therapeutic ratio enhancement.

Original languageEnglish (US)
Title of host publicationEnergy-Based Treatment of Tissue and Assessment VIII
EditorsThomas P. Ryan
PublisherSPIE
ISBN (Electronic)9781628414165
DOIs
StatePublished - 2015
Externally publishedYes
Event2015 SPIE Conference: Energy-Based Treatment of Tissue and Assessment - San Francisco, United States
Duration: Feb 8 2015Feb 9 2015

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume9326
ISSN (Print)1605-7422

Conference

Conference2015 SPIE Conference: Energy-Based Treatment of Tissue and Assessment
Country/TerritoryUnited States
CitySan Francisco
Period2/8/152/9/15

Keywords

  • Iron oxide nanoparticles
  • cancer
  • radiation
  • radiation enhancement

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

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