Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([223Ra]RaCl2): 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

doi:10.3390/cells12030451

Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([²²³Ra]RaCl₂): Understanding the Effect on Cell Structure

Cells. 2023 Jan 31;12(3):451. doi: 10.3390/cells12030451.

Authors

Joel Félix Silva Diniz Filho¹, Aline Oliveira da Silva de Barros², Martha Sahylí Ortega Pijeira², Eduardo Ricci-Junior³, Victor Midlej⁴, Mariana Pelissari Monteiro Aguiar Baroni⁵, Clenilton Costa Dos Santos¹, Luciana Magalhães Rebelo Alencar¹, Ralph Santos-Oliveira^{2

6}

Affiliations

¹ Biophysics and Nanosystems Laboratory, Department of Physics, Federal University of Maranhão, São Luis 65065690, MA, Brazil.
² Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro 21941906, RJ, Brazil.
³ School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941900, RJ, Brazil.
⁴ Laboratory of Structural Biology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro 21040900, RJ, Brazil.
⁵ Department of Natural Science and Mathematics, Federal Institute of Education, Science and Technology (IFSP), Campus São Paulo, São Paulo 01109010, SP, Brazil.
⁶ Laboratory of Radiopharmacy and Nanoradiopharmaceuticals, State University of Rio de Janeiro, Rio de Janeiro 23070200, RJ, Brazil.

Abstract

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.

Keywords: cell death; cell mechanism; radiopharmaceutical; targeted alpha therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alpha Particles / therapeutic use
Cell Membrane
Humans
Neoplasms* / drug therapy
Radioisotopes
Radiopharmaceuticals
Radium* / therapeutic use

Substances

Radiopharmaceuticals
Radium
Radioisotopes

Grants and funding

This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) (Cientista do Nosso Estado: E-26/200.815/2021; Rede NanoSaude: E-26/010.000981/2019, Pesquisa na UEZO: E-26/010.002362/2019; Temáticos: E-26/211.269/2021, Infraestrutura e Pesquisa na UEZO and UERJ: E-26//211.207/2021, Bolsa de Pós Doutorado Senior (PDS): E-26/202.320/2021) CNPq (Bolsa de Produtividade 1B: 301069/2018-2) to Ralph Santos-Oliveira. National Nuclear Energy Commission (Bolsa de Pós-doutorado CNEN: 01341.011064/2021-71) to Martha Sahylí Ortega Pijeira.