Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy
Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of <...
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2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7326 |
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| author | Mariya A. Vorobyeva Maya A. Dymova Darya S. Novopashina Elena V. Kuligina Valentina V. Timoshenko Iaroslav A. Kolesnikov Sergey Yu. Taskaev Vladimir A. Richter Alya G. Venyaminova |
| author_facet | Mariya A. Vorobyeva Maya A. Dymova Darya S. Novopashina Elena V. Kuligina Valentina V. Timoshenko Iaroslav A. Kolesnikov Sergey Yu. Taskaev Vladimir A. Richter Alya G. Venyaminova |
| author_sort | Mariya A. Vorobyeva |
| collection | DOAJ |
| description | Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of <sup>10</sup>B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying <sup>10</sup>B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The <i>closo</i>-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of <sup>10</sup>B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents. |
| first_indexed | 2024-03-10T09:36:58Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:58Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-14130aee5a094fdcb00eef459a5801a22023-11-22T03:56:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214732610.3390/ijms22147326Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture TherapyMariya A. Vorobyeva0Maya A. Dymova1Darya S. Novopashina2Elena V. Kuligina3Valentina V. Timoshenko4Iaroslav A. Kolesnikov5Sergey Yu. Taskaev6Vladimir A. Richter7Alya G. Venyaminova8Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaBudker Institute of Nuclear Physics, Siberian Division of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, RussiaBoron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of <sup>10</sup>B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying <sup>10</sup>B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The <i>closo</i>-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of <sup>10</sup>B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.https://www.mdpi.com/1422-0067/22/14/7326cell-specific aptamershuman glioblastoma cellsboron clustersboron neutron capture therapycancer treatmentdrug delivery |
| spellingShingle | Mariya A. Vorobyeva Maya A. Dymova Darya S. Novopashina Elena V. Kuligina Valentina V. Timoshenko Iaroslav A. Kolesnikov Sergey Yu. Taskaev Vladimir A. Richter Alya G. Venyaminova Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy International Journal of Molecular Sciences cell-specific aptamers human glioblastoma cells boron clusters boron neutron capture therapy cancer treatment drug delivery |
| title | Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy |
| title_full | Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy |
| title_fullStr | Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy |
| title_full_unstemmed | Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy |
| title_short | Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with <i>Closo</i>-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy |
| title_sort | tumor cell specific 2 fluoro rna aptamer conjugated with i closo i dodecaborate as a potential agent for boron neutron capture therapy |
| topic | cell-specific aptamers human glioblastoma cells boron clusters boron neutron capture therapy cancer treatment drug delivery |
| url | https://www.mdpi.com/1422-0067/22/14/7326 |
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