Carborane containing carbonic anhydrase inhibitors for Boron Neutron Capture Therapy of cancer

This study aims to combine the therapeutic effects related to the inhibition of carbonic anhydrase IX (CAIX), an essential enzyme overexpressed by cancer cells such as mesothelioma and breast cancer, with the application of Boron Neutron Capture Therapy (BNCT). BNCT is an alternative binary radiotherapeutic modality proposed for cancer treatment. It consists of the prior accumulation of non-radioactive boron containing agents in the diseased cells followed by irradiation with low-energy neutrons. To this end, sulfonamido-functionalised-carborane (CA-SF) and sulfamate-functionalised-carborane (CA-SFA), which act both as CAIX inhibitors and as boron releasing agents, are used and compared according to their therapeutic effects. The CAIX expression, measured by Western blot analysis, resulted high in both mesothelioma and breast tumours. This result was used to administer a therapeutic dose of boron (> 20μg / g) to the cancer cells. The synergic cytotoxic effects of enzymatic inhibition and neutron irradiation were evaluated in vitro on AB22 and MCF7 tumor cells. This method provides the basis for further in vivo experiments and, as it appears very promising, it needs attention for the design of new therapeutic approaches to cure patients affected by this disease.