Cyclic rgd-functionalized closo-dodecaborate albumin conjugates as integrin targeting boron carriers for neutron capture therapy

Hiroyuki Nakamura, Kazuki Kawai, Kai Nishimura, Satoshi Okada, Shinichi Sato, Minoru Suzuki, Takushi Takata

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclic RGD (cRGD) peptide-conjugated boronated albumin was developed to direct toward integrin αvβ3, which overexpresses on many cancer cells. A stepwise conjugation of c[RGDfK(Mal)] and maleimide-conjugated closo-dodecaborate (MID) to bovine serum albumin (BSA) afforded cRGD-MID-BSA, which was noncytotoxic toward both U87MG and A549 cells. As compared with L-BPA, selective antitumor activity of cRGD-MID-BSA toward U87MG cells overexpressing integrin αvβ3 was identified after thermal neutron irradiation. In vivo fluorescence live imaging of Cy5-conjugated cRGD-MID-BSA and MID-BSA revealed that both cRGD-MID-BSA and MID-BSA similarly reached the maximum accumulation during 8-12 h after injection. The selective accumulation and retention of Cy5-cRGD-MID-BSA was more pronounced than Cy5-MID-BSA after 24 h. An in vivo boron neutron capture therapy (BNCT) study revealed that the cRGD peptide ligand combination enhanced accumulation of MIDBSA into tumor cells in U87MG xenograft models. The significant tumor growth suppression was observed in U87MG xenograft models at a dose of 7.5 mg [10B]/kg after neutron irradiation.

Original languageEnglish
Pages (from-to)3740-3747
Number of pages8
JournalMolecular pharmaceutics
Volume17
Issue number10
DOIs
Publication statusPublished - 2020 Oct 5

Keywords

  • Albumin
  • Boron neutron capture therapy
  • Closo-dodecaborate
  • Cyclic RGD
  • Integrin
  • Tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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