Carborane derivatives loaded into liposomes as efficient delivery systems for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is an anticancer therapy based on the incorporation of 10B in tumors, followed by neutron irradiation. BNCT has been applied all over the world to treat different neoplasias, such as glioblastoma, skin melanoma, head and neck cancer, mesothelioma, and diffuse liver metastases. It represents a valuable option in the treatment of tumors that cannot be removed surgically or when the conventional therapies are ineffective. This is the case, for instance, with diffuse metastases: if the entire organ affected by metastases is irradiated after boron accumulation, all the tumor nodules and single cells are hit, without the need to know their precise number and distribution. The selectivity of BNCT is its main characteristic, and it depends critically on the possibility of obtaining a high ratio of the boron concentration in tumor cells to that in normal ones. Provided a sufficient amount of boron is accumulated in the tumor and a good concentration ratio is attained, the selectivity of the radiation dose delivered does not depend on the neutron irradiation field. Recently, the synthesis and delivery of new boronated compounds have been recognized as some of the main challenges in BNCT application. Here, we report on the use of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl β-lactoside (LCOB) and 1-methyl-o-closocarboranyl-2-hexylthioporphyrazine (H2PzCOB), were loaded into liposomes bearing different surface charges.The efficacy of these formulationswas tested onmodel cell cultures, that is, DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma. These induce liver and lung metastases, respectively, and are used to study the uptake of standard BNCT drugs, including borophenylalanine (BPA). Boron concentration in treated cells was measured by R spectrometry at the TRIGA mark II reactor (University of Pavia). Results showed high performance of the proposed formulations. In particular, the use of cationic liposomes increased the cellular concentration of 10B by at least 30 times more than that achieved by BPA.