Iodophenyl-conjugated closo-dodecaborate as a promising small boron molecule that binds to serum albumin and accumulates in tumor

Abstract

The development of novel boron carriers applicable to various cancers is required for further expansion of boron neutron capture therapy (BNCT). In this study, we took advantage of the fact that serum albumin accumulates in tumors and developed a boron compound that interacts non-covalently with the serum albumin. 4-Iodophenylbutanamide was chosen as an albumin ligand and conjugated with closo-dodecaborate (boron-conjugated 4-iodophenylbutanamide: BC-IP). BC-IP was found to be water soluble with low cytotoxicity. The IC50 values of BC-IP were 475 µM for U87MG cells, 738 µM for HeLa cells, and > 1000 µM for A549 cells. The dissociation constant (Kd) value of BC-IP to HSA was 148 ± 8 μM, while that of disodium closo-dodecaborate (4) was > 1000 μM. Significant tumor accumulation was observed in the U87MG tumor mouse model 3 h after injection. The boron concentration in the tumor reached a maximum of 11 μgB/g at 3 h and gradually decreased to 2.4 and 2.3 μgB/g at 12 and 24 h, respectively.