Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture therapy (BNCT)

Hiroyuki Michiue, Mizuki Kitamatsu, Asami Fukunaga, Nobushige Tsuboi, Atsushi Fujimura, Hiroaki Matsushita, Kazuyo Igawa, Tomonari Kasai, Natsuko Kondo, Hideki Matsui, Shuichi Furuya

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.

Original languageEnglish
Pages (from-to)788-796
Number of pages9
JournalJournal of Controlled Release
Volume330
DOIs
Publication statusPublished - Feb 10 2021
Externally publishedYes

Keywords

  • A6K peptide
  • Boron drug
  • Boron neutron capture therapy (BNCT)
  • Drug delivery system (DDS)
  • Malignant brain tumor
  • Peptide nanotube

ASJC Scopus subject areas

  • Pharmaceutical Science

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