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Michiue, Hiroyuki Neutron Therapy Research Center, Okayama University ORCID Kaken ID publons researchmap
Kitamatsu, Mizuki Department of Applied Chemistry, Kindai University Kaken ID publons researchmap
Fukunaga, Asami Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsuboi, Nobushige Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
Fujimura, Atsushi Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID researchmap
Matsushita, Hiroaki Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Igawa, Kazuyo Neutron Therapy Research Center, Okayama University
Kasai, Tomonari Neutron Therapy Research Center, Okayama University Kaken ID publons researchmap
Kondo, Natsuko Institute for Integrated Radiation and Nuclear Science, Kyoto University
Matsui, Hideki Neutron Therapy Research Center, Okayama University Kaken ID publons researchmap
Furuya, Shuichi Neutron Therapy Research Center, Okayama University
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.
Keywords
Malignant brain tumor
Boron neutron capture therapy (BNCT)
Peptide nanotube
Boron drug
Drug delivery system (DDS)
A6K peptide
Published Date
2020-11-11
Publication Title
Journal of Controlled Release
Volume
volume330
Publisher
Elsevier
Start Page
788
End Page
196
ISSN
0168-3659
NCID
AA10458678
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 The Author(s).
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DOI
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isVersionOf https://doi.org/10.1016/j.jconrel.2020.11.001
License
http://creativecommons.org/licenses/by/4.0/