Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect
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-formi...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/20/3307 |
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| author | Abdul Basith Fithroni Kazuko Kobayashi Hirotaka Uji Manabu Ishimoto Masaru Akehi Takashi Ohtsuki Eiji Matsuura |
| author_facet | Abdul Basith Fithroni Kazuko Kobayashi Hirotaka Uji Manabu Ishimoto Masaru Akehi Takashi Ohtsuki Eiji Matsuura |
| author_sort | Abdul Basith Fithroni |
| collection | DOAJ |
| description | 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 (<i>o-</i>, <i>m-</i>, and <i>p-</i>carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-<i>o-</i>carborane (diC1-Carb), 1,2-dihexyl-<i>o-</i>carborane (diC6-Carb), and 1,2-didodecyl-<i>o-</i>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. |
| first_indexed | 2024-03-09T20:29:08Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T20:29:08Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-68a8bfb420814ca387b6702d77dde3022023-11-23T23:28:56ZengMDPI AGCells2073-44092022-10-011120330710.3390/cells11203307Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue EffectAbdul Basith Fithroni0Kazuko Kobayashi1Hirotaka Uji2Manabu Ishimoto3Masaru Akehi4Takashi Ohtsuki5Eiji Matsuura6Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanCollaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, JapanFukushima SiC Applied Engineering Inc., Naraha-machi 979-0513, JapanCollaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanDepartment of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanDepartment of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, JapanBNCT 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 (<i>o-</i>, <i>m-</i>, and <i>p-</i>carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-<i>o-</i>carborane (diC1-Carb), 1,2-dihexyl-<i>o-</i>carborane (diC6-Carb), and 1,2-didodecyl-<i>o-</i>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.https://www.mdpi.com/2073-4409/11/20/3307boron neutron capture therapy (BNCT)biologically self-degradable amphipathic polymer (Lactosome)hydrophobic boron clustercarborane isomers or <i>o</i>-carborane alkylated derivativesmolecular glue effect |
| spellingShingle | Abdul Basith Fithroni Kazuko Kobayashi Hirotaka Uji Manabu Ishimoto Masaru Akehi Takashi Ohtsuki Eiji Matsuura Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect Cells boron neutron capture therapy (BNCT) biologically self-degradable amphipathic polymer (Lactosome) hydrophobic boron cluster carborane isomers or <i>o</i>-carborane alkylated derivatives molecular glue effect |
| title | Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect |
| title_full | Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect |
| title_fullStr | Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect |
| title_full_unstemmed | Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect |
| title_short | Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect |
| title_sort | novel self forming nanosized dds particles for bnct utilizing a hydrophobic boron cluster and its molecular glue effect |
| topic | boron neutron capture therapy (BNCT) biologically self-degradable amphipathic polymer (Lactosome) hydrophobic boron cluster carborane isomers or <i>o</i>-carborane alkylated derivatives molecular glue effect |
| url | https://www.mdpi.com/2073-4409/11/20/3307 |
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