Folic acid-conjugated 4-amino-phenylboronate, a boron-containing compound designed for boron neutron capture therapy, is an unexpected agonist for human neutrophils and platelets

Boron neutron capture therapy (BNCT) is an anticancer treatment based on the accumulation in the tumor cells of 10B-containing molecules and subsequent irradiation with low-energy neutrons, which bring about the decay of 10B to very toxic 7Li3+ and 4He 2+ ions. The effectiveness of BNCT is limited by the low delivery and accumulation of the used 10B-containing compounds. Here, we report the development of folic acid-conjugated 4-amino-phenylboronate as a novel possible compound for the selective delivery of 10B in BNCT. An extensive analysis about its biocompatibility to mature blood cells and platelet progenitors revealed that the compound markedly supports platelet aggregation, neutrophil oxidative burst, and inhibition of megakaryocyte development, while it does not have any manifest effect on red blood cells. 4-amino-phenylboronate conjugated with folic acid is a possible compound for selective delivery of 10B in boron neutron capture therapy. Its biocompatibility with blood cells was tested. It was completely inert toward erythrocytes, whereas it induced platelet aggregation, neutrophil oxidative burst, and inhibition of platelet progenitor (megakaryocyte) development. Folic acid and 4-amino-phenylboronate are each essentially inert toward blood cells. A new property, which was not present in either of the reactants, appeared in the adduct. © 2013 John Wiley & Sons A/S.