Assessment of Carrier-Free Metallacarboranes for Targeted Radiation Therapies PBFT and BNCT: Comparative Cellular Effects and Dosimetry Studies with [o-FESAN]− in Breast Cancer Cells

<b>Background:</b> Ferrabis(dicarbollide) ([<i>o</i>-FESAN]^-) in combination with proton-boron fusion therapy (PBFT) or boron neutron capture therapy (BNCT) are promising alternative radiation modalities for the treatment of breast cancer. The aim of this study was to explore the underlying effects of [<i>o</i>-FESAN]^- radio enhancement on breast cancer cells in vitro and in vivo, and to perform comparative dosimetry calculations. <b>Methods:</b> The cellular effects on SKBR-3 and MDA-MB-231 breast cancer cells and MDA-MB-231 xenograft-bearing nude mice induced by carrier-free [<i>o</i>-FESAN]^- after BNCT or PBFT were evaluated following recommended protocols. Monte Carlo (MC) dosimetry calculations were performed at the cellular scale for both radiation modalities. <b>Results:</b> Selective retention of [<i>o</i>-FESAN]^- within the cytoplasm and nucleus of SKBR-3 and MDA-MB-231 breast cancer cells is demonstrated. Moreover, in vivo studies with MDA-MB-231 xenograft-bearing nude mice show appreciable accumulation of [<i>o</i>-FESAN]^- in the tumor. Both radiation modalities induce loss of cellular viability and survival. Comparative dosimetry studies between proton and neutron irradiation agree with the viability data, showing a good correlation between absorbed dose vs. cellular effects. In the case of PBFT, cell structural changes are likely due to necrosis caused by the production of reactive oxygen species (ROS). To explain the radio enhancement effects in more detail, other mechanisms should be taken into consideration. <b>Conclusions:</b> Our results validate the effectiveness of both PBFT and BNCT therapeutic modalities, warranting further studies on carrier-free [<i>o</i>-FESAN]^- as a candidate drug for potential clinical translation of radio enhancers in binary radiation therapies.