BACKGROUND: Protons, which are considered low-LET (Linear Energy Transfer) radiation, have an average RBE (relative biological effectiveness) of 1.1, with a range from 0.7 to 1.6. Thus, increasing biological effectiveness is of high interest in radiation oncology, and one way to enhance this is by using radiosensitizers. The present work investigates the effectiveness of the proton boron fusion reaction (PBFR) at the cellular level, using the sodium salt of metallacarborane [3,3'-Co(C2B9H11)2] RESULTS: MDA-MB-231 breast cancer cells were used. Nuclear microscopy assessed [o-COSAN] uptake and distribution in single cells, while biodistribution was studied in tumor-bearing Balb/cSlc-nu/nu mice (MDA-MB-231 xenograft), with boron accumulation in target organs and tumor measured by ICP-OES. The cells were irradiated with a proton beam tuned to reach the PBFR resonance energy of 675 keV at the cell layer. DNA damage was assessed with the g-H2AX assay and cell survival with the clonogenic assay. Beam parameters and dose calibration curves using radiochromic films validated Monte Carlo dosimetry simulations. As expected, we observed higher biological damage in irradiated cells and the presence of [o-COSAN] CONCLUSIONS: The radiosensitizing effect of [o-COSAN]