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
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
Affiliations
Joel Félix Silva Diniz Filho
Biophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, Brazil
Aline Oliveira da Silva de Barros
Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, Brazil
Martha Sahylí Ortega Pijeira
Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, Brazil
Eduardo Ricci-Junior
School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941900, RJ, Brazil
Victor Midlej
Laboratory of Structural Biology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro 21040900, RJ, Brazil
Mariana Pelissari Monteiro Aguiar Baroni
Department of Natural Science and Mathematics, Federal Institute of Education, Science and Technology (IFSP), Campus São Paulo, São Paulo 01109010, SP, Brazil
Clenilton Costa dos Santos
Biophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, Brazil
Luciana Magalhães Rebelo Alencar
Biophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, Brazil
Ralph Santos-Oliveira
Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, Brazil
The use of alpha-particle (α-particle) radionuclides, especially [223Ra]RaCl2 (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 [223Ra] RaCl2 on cancer cells. To analyze the effect of [223Ra]RaCl2 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.
