1. Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)
- Author
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Natsuko Kondo, Tomonari Kasai, Hiroaki Matsushita, Kazuyo Igawa, Mizuki Kitamatsu, Asami Fukunaga, Shuichi Furuya, Nobushige Tsuboi, Hideki Matsui, Atsushi Fujimura, and Hiroyuki Michiue
- Subjects
Boron Compounds ,Nanotubes, Peptide ,inorganic chemicals ,Pharmaceutical Science ,chemistry.chemical_element ,Boron Neutron Capture Therapy ,Peptide ,Borohydrides ,02 engineering and technology ,Mice ,03 medical and health sciences ,Transduction (genetics) ,Boron drug ,Pharmacokinetics ,Glioma ,medicine ,Animals ,Humans ,Sulfhydryl Compounds ,Boron ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Nanotubes ,Chemistry ,Cell growth ,Drug delivery system (DDS) ,021001 nanoscience & nanotechnology ,medicine.disease ,Malignant brain tumor ,Peptide nanotube ,Boron neutron capture therapy (BNCT) ,A6K peptide ,Drug delivery ,Cancer research ,0210 nano-technology ,Oligopeptides ,Intracellular - 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.
- Published
- 2020