Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure
The use of alpha-particle (α-particle) radionuclides, especially [<sup>223</sup>Ra]RaCl<sub>2</sub> (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/3/451 |
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| author | Joel Félix Silva Diniz Filho Aline Oliveira da Silva de Barros Martha Sahylí Ortega Pijeira Eduardo Ricci-Junior Victor Midlej Mariana Pelissari Monteiro Aguiar Baroni Clenilton Costa dos Santos Luciana Magalhães Rebelo Alencar Ralph Santos-Oliveira |
| author_facet | Joel Félix Silva Diniz Filho Aline Oliveira da Silva de Barros Martha Sahylí Ortega Pijeira Eduardo Ricci-Junior Victor Midlej Mariana Pelissari Monteiro Aguiar Baroni Clenilton Costa dos Santos Luciana Magalhães Rebelo Alencar Ralph Santos-Oliveira |
| author_sort | Joel Félix Silva Diniz Filho |
| collection | DOAJ |
| description | The use of alpha-particle (α-particle) radionuclides, especially [<sup>223</sup>Ra]RaCl<sub>2</sub> (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [<sup>223</sup>Ra] RaCl<sub>2</sub> on cancer cells. To analyze the effect of [<sup>223</sup>Ra]RaCl<sub>2</sub> on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy. |
| first_indexed | 2024-03-11T09:49:29Z |
| format | Article |
| id | doaj.art-cbb242b5c6864f93add2613aff322b66 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T09:49:29Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cbb242b5c6864f93add2613aff322b662023-11-16T16:21:49ZengMDPI AGCells2073-44092023-01-0112345110.3390/cells12030451Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell StructureJoel Félix Silva Diniz Filho0Aline Oliveira da Silva de Barros1Martha Sahylí Ortega Pijeira2Eduardo Ricci-Junior3Victor Midlej4Mariana Pelissari Monteiro Aguiar Baroni5Clenilton Costa dos Santos6Luciana Magalhães Rebelo Alencar7Ralph Santos-Oliveira8Biophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, BrazilLaboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, BrazilLaboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, BrazilSchool of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941900, RJ, BrazilLaboratory of Structural Biology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro 21040900, RJ, BrazilDepartment of Natural Science and Mathematics, Federal Institute of Education, Science and Technology (IFSP), Campus São Paulo, São Paulo 01109010, SP, BrazilBiophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, BrazilBiophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, BrazilLaboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, BrazilThe use of alpha-particle (α-particle) radionuclides, especially [<sup>223</sup>Ra]RaCl<sub>2</sub> (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [<sup>223</sup>Ra] RaCl<sub>2</sub> on cancer cells. To analyze the effect of [<sup>223</sup>Ra]RaCl<sub>2</sub> on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy.https://www.mdpi.com/2073-4409/12/3/451cell deathcell mechanismtargeted alpha therapyradiopharmaceutical |
| spellingShingle | Joel Félix Silva Diniz Filho Aline Oliveira da Silva de Barros Martha Sahylí Ortega Pijeira Eduardo Ricci-Junior Victor Midlej Mariana Pelissari Monteiro Aguiar Baroni Clenilton Costa dos Santos Luciana Magalhães Rebelo Alencar Ralph Santos-Oliveira Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure Cells cell death cell mechanism targeted alpha therapy radiopharmaceutical |
| title | Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure |
| title_full | Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure |
| title_fullStr | Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure |
| title_full_unstemmed | Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure |
| title_short | Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([<sup>223</sup>Ra]RaCl<sub>2</sub>): Understanding the Effect on Cell Structure |
| title_sort | ultrastructural analysis of cancer cells treated with the radiopharmaceutical radium dichloride sup 223 sup ra racl sub 2 sub understanding the effect on cell structure |
| topic | cell death cell mechanism targeted alpha therapy radiopharmaceutical |
| url | https://www.mdpi.com/2073-4409/12/3/451 |
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