start-ver=1.4 cd-journal=joma no-vol=330 cd-vols= no-issue= article-no= start-page=788 end-page=196 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT) en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KitamatsuMizuki en-aut-sei=Kitamatsu en-aut-mei=Mizuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukunagaAsami en-aut-sei=Fukunaga en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboiNobushige en-aut-sei=Tsuboi en-aut-mei=Nobushige kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=FujimuraAtsushi en-aut-sei=Fujimura en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsushitaHiroaki en-aut-sei=Matsushita en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IgawaKazuyo en-aut-sei=Igawa en-aut-mei=Kazuyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KondoNatsuko en-aut-sei=Kondo en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuiHideki en-aut-sei=Matsui en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=FuruyaShuichi en-aut-sei=Furuya en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=2 en-affil=Department of Applied Chemistry, Kindai University kn-affil= affil-num=3 en-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=8 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=9 en-affil=Institute for Integrated Radiation and Nuclear Science, Kyoto University kn-affil= affil-num=10 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= affil-num=11 en-affil=Neutron Therapy Research Center, Okayama University kn-affil= en-keyword=Malignant brain tumor kn-keyword=Malignant brain tumor en-keyword=Boron neutron capture therapy (BNCT) kn-keyword=Boron neutron capture therapy (BNCT) en-keyword=Peptide nanotube kn-keyword=Peptide nanotube en-keyword=Boron drug kn-keyword=Boron drug en-keyword=Drug delivery system (DDS) kn-keyword=Drug delivery system (DDS) en-keyword=A6K peptide kn-keyword=A6K peptide END start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue=9 article-no= start-page=e107976 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140929 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation en-subtitle= kn-subtitle= en-abstract= kn-abstract=Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside. en-copyright= kn-copyright= en-aut-name=ShigehiroTsukasa en-aut-sei=Shigehiro en-aut-mei=Tsukasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MurakamiMasaharu en-aut-sei=Murakami en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SekharSreeja C. en-aut-sei=Sekhar en-aut-mei=Sreeja C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TominagaYuki en-aut-sei=Tominaga en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaMasashi en-aut-sei=Okada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KudohTakayuki en-aut-sei=Kudoh en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizutaniAkifumi en-aut-sei=Mizutani en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiHiroshi en-aut-sei=Murakami en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SalomonDavid S. en-aut-sei=Salomon en-aut-mei=David S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MikuniKatsuhiko en-aut-sei=Mikuni en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MandaiTadakatsu en-aut-sei=Mandai en-aut-mei=Tadakatsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=HamadaHiroki en-aut-sei=Hamada en-aut-mei=Hiroki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=2 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=3 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=4 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=5 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=6 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=7 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=8 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=9 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University affil-num=10 en-affil= kn-affil=Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute affil-num=11 en-affil= kn-affil=Ensuiko Sugar Refining Co., Ltd. affil-num=12 en-affil= kn-affil=Faculty of Life Science, Kurashiki University of Science and the Arts affil-num=13 en-affil= kn-affil=Faculty of Science, Okayama University of Science affil-num=14 en-affil= kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=4 article-no= start-page=e33544 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120412 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5'-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model. en-copyright= kn-copyright= en-aut-name=ChenLing en-aut-sei=Chen en-aut-mei=Ling kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KasaiTomonari en-aut-sei=Kasai en-aut-mei=Tomonari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiYueguang en-aut-sei=Li en-aut-mei=Yueguang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SugiiYuh en-aut-sei=Sugii en-aut-mei=Yuh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=JinGuoliang en-aut-sei=Jin en-aut-mei=Guoliang kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaMasashi en-aut-sei=Okada en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=VaidyanathArun en-aut-sei=Vaidyanath en-aut-mei=Arun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MizutaniAkifumi en-aut-sei=Mizutani en-aut-mei=Akifumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=SatohAyano en-aut-sei=Satoh en-aut-mei=Ayano kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KudohTakayuki en-aut-sei=Kudoh en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HendrixMary J. C. en-aut-sei=Hendrix en-aut-mei=Mary J. C. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SalomonDavid S en-aut-sei=Salomon en-aut-mei=David S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=FuLi en-aut-sei=Fu en-aut-mei=Li kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SenoMasaharu en-aut-sei=Seno en-aut-mei=Masaharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ affil-num=2 en-affil= kn-affil=Okayama Univ affil-num=3 en-affil= kn-affil=Tianjin 4th Ctr Hosp affil-num=4 en-affil= kn-affil=Okayama Univ affil-num=5 en-affil= kn-affil=Okayama Univ affil-num=6 en-affil= kn-affil=Okayama Univ affil-num=7 en-affil= kn-affil=Okayama Univ affil-num=8 en-affil= kn-affil=Okayama Univ affil-num=9 en-affil= kn-affil=Okayama Univ affil-num=10 en-affil= kn-affil=Okayama Univ affil-num=11 en-affil= kn-affil=Northwestern Univ affil-num=12 en-affil= kn-affil=NCI affil-num=13 en-affil= kn-affil=Tianjin Med Univ affil-num=14 en-affil= kn-affil=Okayama Univ END