Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model
Integrin α<sub>v</sub>β<sub>3</sub> is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized <i>closo</i>-dodecaborate (MID), serum albumin as a drug delivery system, an...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/3/377 |
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| author | Kohei Tsujino Hideki Kashiwagi Kai Nishimura Ryo Kayama Kohei Yoshimura Yusuke Fukuo Hiroyuki Shiba Ryo Hiramatsu Naosuke Nonoguchi Motomasa Furuse Toshihiro Takami Shin-Ichi Miyatake Naonori Hu Takushi Takata Hiroki Tanaka Minoru Suzuki Shinji Kawabata Hiroyuki Nakamura Masahiko Wanibuchi |
| author_facet | Kohei Tsujino Hideki Kashiwagi Kai Nishimura Ryo Kayama Kohei Yoshimura Yusuke Fukuo Hiroyuki Shiba Ryo Hiramatsu Naosuke Nonoguchi Motomasa Furuse Toshihiro Takami Shin-Ichi Miyatake Naonori Hu Takushi Takata Hiroki Tanaka Minoru Suzuki Shinji Kawabata Hiroyuki Nakamura Masahiko Wanibuchi |
| author_sort | Kohei Tsujino |
| collection | DOAJ |
| description | Integrin α<sub>v</sub>β<sub>3</sub> is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized <i>closo</i>-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin α<sub>v</sub>β<sub>3</sub> was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin α<sub>v</sub>β<sub>3</sub> in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA. |
| first_indexed | 2024-03-11T06:54:46Z |
| format | Article |
| id | doaj.art-a7bc0b20abaa4d65afacab7351280544 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T06:54:46Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-a7bc0b20abaa4d65afacab73512805442023-11-17T09:41:19ZengMDPI AGBiology2079-77372023-02-0112337710.3390/biology12030377Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma ModelKohei Tsujino0Hideki Kashiwagi1Kai Nishimura2Ryo Kayama3Kohei Yoshimura4Yusuke Fukuo5Hiroyuki Shiba6Ryo Hiramatsu7Naosuke Nonoguchi8Motomasa Furuse9Toshihiro Takami10Shin-Ichi Miyatake11Naonori Hu12Takushi Takata13Hiroki Tanaka14Minoru Suzuki15Shinji Kawabata16Hiroyuki Nakamura17Masahiko Wanibuchi18Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanKansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanKansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, JapanInstitute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanLaboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, JapanDepartment of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, JapanIntegrin α<sub>v</sub>β<sub>3</sub> is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized <i>closo</i>-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin α<sub>v</sub>β<sub>3</sub> was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin α<sub>v</sub>β<sub>3</sub> in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA.https://www.mdpi.com/2079-7737/12/3/377boron neutron capture therapy (BNCT)gliomaintegrincyclic arginine-glycine-aspartatebiological targetalbumin |
| spellingShingle | Kohei Tsujino Hideki Kashiwagi Kai Nishimura Ryo Kayama Kohei Yoshimura Yusuke Fukuo Hiroyuki Shiba Ryo Hiramatsu Naosuke Nonoguchi Motomasa Furuse Toshihiro Takami Shin-Ichi Miyatake Naonori Hu Takushi Takata Hiroki Tanaka Minoru Suzuki Shinji Kawabata Hiroyuki Nakamura Masahiko Wanibuchi Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model Biology boron neutron capture therapy (BNCT) glioma integrin cyclic arginine-glycine-aspartate biological target albumin |
| title | Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model |
| title_full | Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model |
| title_fullStr | Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model |
| title_full_unstemmed | Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model |
| title_short | Improved Boron Neutron Capture Therapy Using Integrin αvβ3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model |
| title_sort | improved boron neutron capture therapy using integrin αvβ3 targeted long retention type boron carrier in a f98 rat glioma model |
| topic | boron neutron capture therapy (BNCT) glioma integrin cyclic arginine-glycine-aspartate biological target albumin |
| url | https://www.mdpi.com/2079-7737/12/3/377 |
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