The Mössbauer effect using 57Fe-ferrabisdicarbollide ([o-57FESAN]−): a glance into the potential of a low-dose approach for glioblastoma radiotherapy

Abstract

Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. To overcome this situation, more effective and selective treatments are necessary using anti-tumour agents that act in two or more ways and offer greater therapeutic benefits over single-mechanism entities. In this study, we report on treating cancer with Na[3,3′-⁵⁷Fe(1,2-C₂B₉H₁₁)₂], which offers the possibility of dual action (radiation–drug combinations) to improve the clinical benefits and reduce healthy tissue toxicity. An approach to evaluating the potential of [o-⁵⁷FESAN]⁻ to treat glioblastoma using the Mössbauer effect is presented. As the therapeutic outcomes rely on the amount and distribution of [o-⁵⁷FESAN]⁻ inside the cells, several studies, using magnetization, Mössbauer spectroscopy and nuclear microscopy techniques, were performed to ascertain the uptake of [o-⁵⁷FESAN]⁻ in U87 glioblastoma cells. [o-⁵⁷FESAN]⁻ was found to be within the cells; 29% of its uptake was in the nuclear fraction, which is a particularly desirable target, because the nucleus is the cell's control centre where DNA and the transcription machinery reside. Irradiation studies with 2D and 3D cellular models of U87 cells showed that the growth inhibition effect observed was more pronounced when [o-⁵⁷FESAN]⁻ was used in combination with the Mössbauer effect in low total dose regimens, suggesting that this procedure either alone or as adjuvant may be useful for glioblastoma treatment.