ID | 64013 |
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Fithroni, Abdul Basith
Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Kobayashi, Kazuko
Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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Uji, Hirotaka
Department of Material Chemistry, Graduate School of Engineering, Kyoto University
Ishimoto, Manabu
Fukushima SiC Applied Engineering Inc.
Akehi, Masaru
Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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Ohtsuki, Takashi
Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Matsuura, Eiji
Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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Abstract | BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT.
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Keywords | boron neutron capture therapy (BNCT)
biologically self-degradable amphipathic polymer (Lactosome)
hydrophobic boron cluster
carborane isomers or o-carborane alkylated derivatives
molecular glue effect
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Published Date | 2022-10-21
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Publication Title |
CELLS
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Volume | volume11
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Issue | issue20
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Publisher | MDPI
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Start Page | 3307
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ISSN | 2073-4409
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2022 by the authors.
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File Version | publisher
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DOI | |
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Related Url | isVersionOf https://doi.org/10.3390/cells11203307
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License | https://creativecommons.org/licenses/by/4.0/
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