Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy
Boron neutron capture therapy (BNCT) induces intracellular nuclear reaction to destroy cancer cells during thermal neutron irradiation. To selectively eliminate cancer cells but avoid harmful effects on normal tissues, novel boron-peptide conjugates with angiopep-2, namely ANG-B, were constructed an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1199881/full |
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| author | Jing Xiang Lin Ma Jianfei Tong Jianfei Tong Nan Zuo Nan Zuo Weitao Hu Yupeng Luo Junqi Liu Tianjiao Liang Tianjiao Liang Qiushi Ren Qiushi Ren Qi Liu Qi Liu |
| author_facet | Jing Xiang Lin Ma Jianfei Tong Jianfei Tong Nan Zuo Nan Zuo Weitao Hu Yupeng Luo Junqi Liu Tianjiao Liang Tianjiao Liang Qiushi Ren Qiushi Ren Qi Liu Qi Liu |
| author_sort | Jing Xiang |
| collection | DOAJ |
| description | Boron neutron capture therapy (BNCT) induces intracellular nuclear reaction to destroy cancer cells during thermal neutron irradiation. To selectively eliminate cancer cells but avoid harmful effects on normal tissues, novel boron-peptide conjugates with angiopep-2, namely ANG-B, were constructed and evaluated in preclinical settings. Boron-peptide conjugates were synthesized using solid-phase peptide synthesis, and the molecular mass was validated by mass spectrometry afterwards. Boron concentrations in 6 cancer cell lines and an intracranial glioma mouse model after treatments were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Phenylalanine (BPA) was tested in parallel for comparison. In vitro treatment with boron delivery peptides significantly increased boron uptake in cancer cells. BNCT with 5 mM ANG-B caused 86.5% ± 5.3% of clonogenic cell death, while BPA at the same concentration caused 73.3% ± 6.0% clonogenic cell death. The in vivo effect of ANG-B in an intracranial glioma mouse model was evaluated by PET/CT imaging at 31 days after BNCT. The mouse glioma tumours in the ANG-B-treated group were shrunk by 62.9% on average, while the BPA-treated tumours shrank by only 23.0%. Therefore, ANG-B is an efficient boron delivery agent, which has low cytotoxicity and high tumour-to-blood ratio. Based on these experimental results, we expected that ANG-B may leverage BNCT performance in clinical applications in future. |
| first_indexed | 2024-03-13T08:07:12Z |
| format | Article |
| id | doaj.art-3eef714b9bd3467fbd5a8a83f1cf67fc |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-13T08:07:12Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-3eef714b9bd3467fbd5a8a83f1cf67fc2023-06-01T04:34:34ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-06-011010.3389/fmed.2023.11998811199881Boron-peptide conjugates with angiopep-2 for boron neutron capture therapyJing Xiang0Lin Ma1Jianfei Tong2Jianfei Tong3Nan Zuo4Nan Zuo5Weitao Hu6Yupeng Luo7Junqi Liu8Tianjiao Liang9Tianjiao Liang10Qiushi Ren11Qiushi Ren12Qi Liu13Qi Liu14Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, ChinaDepartment of Stomatology, General Hospital, Shenzhen University, Shenzhen, Guangdong, ChinaInstitute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, ChinaSpallation Neutron Source Science Center, Dongguan, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, Guangdong, ChinaDepartment of Stomatology, The First Hospital, Harbin Medical University, Harbin, ChinaSchool of Stomatology, Hangzhou Normal University, Hangzhou, Zhejiang, ChinaSchool of Stomatology, Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaInstitute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, ChinaSpallation Neutron Source Science Center, Dongguan, ChinaInstitute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China0International Cancer Center, Shenzhen University School of Medicine, Shenzhen University, Shenzhen, Guangdong, ChinaInstitute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, Guangdong, ChinaBoron neutron capture therapy (BNCT) induces intracellular nuclear reaction to destroy cancer cells during thermal neutron irradiation. To selectively eliminate cancer cells but avoid harmful effects on normal tissues, novel boron-peptide conjugates with angiopep-2, namely ANG-B, were constructed and evaluated in preclinical settings. Boron-peptide conjugates were synthesized using solid-phase peptide synthesis, and the molecular mass was validated by mass spectrometry afterwards. Boron concentrations in 6 cancer cell lines and an intracranial glioma mouse model after treatments were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Phenylalanine (BPA) was tested in parallel for comparison. In vitro treatment with boron delivery peptides significantly increased boron uptake in cancer cells. BNCT with 5 mM ANG-B caused 86.5% ± 5.3% of clonogenic cell death, while BPA at the same concentration caused 73.3% ± 6.0% clonogenic cell death. The in vivo effect of ANG-B in an intracranial glioma mouse model was evaluated by PET/CT imaging at 31 days after BNCT. The mouse glioma tumours in the ANG-B-treated group were shrunk by 62.9% on average, while the BPA-treated tumours shrank by only 23.0%. Therefore, ANG-B is an efficient boron delivery agent, which has low cytotoxicity and high tumour-to-blood ratio. Based on these experimental results, we expected that ANG-B may leverage BNCT performance in clinical applications in future.https://www.frontiersin.org/articles/10.3389/fmed.2023.1199881/fullBoron neutron capture therapy (BNCT)boron-peptide conjugatesangiopep-2binary radiation therapycancer medicine |
| spellingShingle | Jing Xiang Lin Ma Jianfei Tong Jianfei Tong Nan Zuo Nan Zuo Weitao Hu Yupeng Luo Junqi Liu Tianjiao Liang Tianjiao Liang Qiushi Ren Qiushi Ren Qi Liu Qi Liu Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy Frontiers in Medicine Boron neutron capture therapy (BNCT) boron-peptide conjugates angiopep-2 binary radiation therapy cancer medicine |
| title | Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy |
| title_full | Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy |
| title_fullStr | Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy |
| title_full_unstemmed | Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy |
| title_short | Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy |
| title_sort | boron peptide conjugates with angiopep 2 for boron neutron capture therapy |
| topic | Boron neutron capture therapy (BNCT) boron-peptide conjugates angiopep-2 binary radiation therapy cancer medicine |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1199881/full |
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