Development of Albumin-closo-Dodecaborate Conjugates as Boron Carriers for Neutron-Capture Therapy by Ru(bpy)3-Photocatalyzed Modification of Tyrosine

Shinichi Sato, Satomu Ishii, Hiroyuki Nakamura

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4406-4410
Number of pages5
JournalEuropean Journal of Inorganic Chemistry
Volume2017
Issue number38
DOIs
Publication statusPublished - 2017 Oct 25
Externally publishedYes

Keywords

  • Boron
  • Neutron capture therapy
  • Photocatalysis
  • Protein modifications
  • Ruthenium

ASJC Scopus subject areas

  • Inorganic Chemistry

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