Arene ruthenium dithiolato–carborane complexes for boron neutron capture therapy (BNCT)

摘要

We report the effect of low-energy thermal neutron irradiation on the antiproliferative activities of a highly hydrophobic organometallic arene ruthenium dithiolato–carborane complex [Ru(p-cymene) (1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1), and of its formulation in Pluronic® triblock copolymer P123 core–shell micelles (RuMs). Complex 1 was highly active, with and without neutron irradiation, towards human ovarian cancer cells (A2780; IC50 0.14 μM and 0.17 μM, respectively) and cisplatin-resistant human ovarian cancer cells (A2780cisR; IC50 0.05 and 0.13 μM, respectively). Complex 1 was particularly sensitive to neutron irradiation in A2780cisR cells (2.6 × more potent after irradiation compared to non-irradiation). Although less potent, the encapsulated complex 1 as RuMs nanoparticles resulted in higher cellular accumulation (2.5×), and was sensitive to neutron irradiation in A2780 cells (1.4× more potent upon irradiation compared to non-irradiation).