Serum albumin has attracted significant attention as a drug-delivery carrier to tumor tissue. We previously reported boron neutron capture therapy (BNCT), an effective method that uses maleimide-functionalized closo-dodecaborate albumin conjugates (MID-ACs). MID can form covalent bonds with the free thiol group of Cys34 and with lysine residues in albumin. In this study, we synthesized tyrosyl-radical-trapping-moiety-functionalized closo-dodecaborates (TRT-DBs), which were expected to form covalent bonds with tyrosine residues. N′-Acetyl-N,N-dimethylphenylenediamine was chosen as the TRT moiety to bind to closo-dodecaborate through an amide linker (TRT-DB 1) and an ammonium linker (TRT-DB 2). TRT-DB 1 more efficiently conjugated to bovine serum albumin (BSA) than 2: approximately 2.4 molecules of 1 were bound to each BSA if BSA (10 µm) was treated with 1 (1 mm) in the presence of Ru(bpy)3 (1 mm; bpy = 2,2′-bipyridyl) and ammonium persulfate (1 mm) under light irradiation for 1 min. Furthermore, double modification of BSA with 1 and MID increased the boron density in BSA for efficient boron delivery to tumors. Western blot analysis using the anti-B12 cluster antibody revealed that closo-dodecaborate-conjugated BSAs were taken up by colon 26 cells.
- Neutron capture therapy
- Protein modifications