Abstract
The synergy of superparamagnetic iron oxide nanoparticles (SPIONs) and ionizing radiation (IR), attributed to reactive oxygen species (ROS) and DNA double-strand breaks (DSBs) increase, was widely investigated in different cancers, but scarcely in melanoma. Herein, SPIONs were evaluated as radiosensitizers in A-375 human melanoma cells. Moreover, the effect of the combined treatment of SPIONs and gamma irradiation (SPIONs-IR) was assessed at the DNA level, where DSBs induction and their repair capacity were studied. SPIONs were synthesized, stabilized by poly(ethylene glycol) methyl ether and physicochemically characterized by high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction and magnetometry and dynamic light scattering. The obtained nanoparticles showing superparamagnetic behavior and low dispersion in shape and sizes were tested in A-375 cells. The intracellular internalization of SPIONs was verified by HR-TEM and quantified by inductively coupled plasma atomic emission spectroscopy. Cells treated with SPIONs exhibited high ROS levels without associated cytotoxicity. Next, a significant radiosensitization in SPIONs-IR vs. control (IR) cells was demonstrated at 1 Gy of gamma radiation. Furthermore, a decreased DSBs repair capacity in SPIONs-IR vs. IR-treated cells was evidenced by the size increase of persistent phosphorylated H2AX foci at 24 h post-irradiation. In conclusion, these nanoparticles show the potential to radiosensitize melanoma cells by the induction of unrepairable DNA damage.
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Acknowledgements
The authors wish to thank Dr. Andrés J. Kreiner from Subgerencia de Tecnología y Aplicaciones de Aceleradores, Gerencia de Investigación y Aplicaciones, CNEA, Dr. Ana María Llois from Instituto de Nanociencia y Nanotecnología, CNEA-CONICET, Dr. Rubén Fernández from Laboratorio de Radiodosimetría Biológica and to the members of División Bioquímica Nuclear, Departamento de Radiobiología, CNEA, for their support; to CEBIRSA S.A. (Argentina) for the irradiation service and to Dr. Carlos Bertoli from Instituto de Nanociencia y Nanotecnología, CNEA-CONICET, Nodo Bariloche, for processing the melanoma cells samples for TEM.
Funding
This work was supported by Comisión Nacional de Energía Atómica, Argentina; Instituto de Nanociencia y Nanotecnología, CNEA-CONICET, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (PIP-11220170100098CO; PUE INN 2018) and by Agencia Nacional de Promoción Científica y Tecnológica, Argentina (PICT 2017-2478; PICT 2017-1239; PICT 2017-2519).
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CG: Formal analysis; Investigation; Methodology; Validation; Visualization; Writing—original draft; Writing—review & editing. MTP: Conceptualization; Formal analysis; Funding acquisition; Investigation; Methodology; Resources; Supervision; Validation; Writing—original draft; Writing—review & editing. MP: Formal analysis; Investigation; Methodology; Resources; Supervision; Validation; Writing—original draft; Writing—review & editing. MA: Investigation; Methodology; Writing—review & editing. LN: Formal analysis; Investigation; Methodology; Writing—review & editing. MSM: Formal analysis; Investigation; Methodology; Validation; Visualization; Writing—review & editing. JS: Investigation; Methodology; Visualization; Writing—review & editing. MSO: Investigation; Methodology; Visualization; Writing—review & editing. MdG: Formal analysis; Funding acquisition; Investigation; Methodology; Resources; Supervision; Validation; Writing—review & editing. HD: Conceptualization; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Writing—original draft; Writing—review & editing. ILI: Conceptualization; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Visualization; Writing—original draft; Writing—review & editing.
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Grissi, C., Taverna Porro, M., Perona, M. et al. Superparamagnetic iron oxide nanoparticles induce persistent large foci of DNA damage in human melanoma cells post-irradiation. Radiat Environ Biophys 62, 357–369 (2023). https://doi.org/10.1007/s00411-023-01037-0
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DOI: https://doi.org/10.1007/s00411-023-01037-0