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<p>Melanoma is considered one of the most radioresistant types of cancer. Enhancing the therapeutic effect of ionizing radiation using nanoparticles is an advanced strategy for modern radiotherapy of solid tumors. This study presents the results of an analysis of the radiosensitizing effect of lutetium fluoride nanoparticles (LuF<sub>3</sub> NPs) on a culture of B16/F10 melanoma cells exposed to X-rays. A comprehensive analysis of the physicochemical properties, intracellular accumulation, and cytotoxicity of LuF<sub>3</sub> NPs was performed, as well as an assessment of their radiocatalytic activity and radiosensitizing effect in vitro. The elemental composition and crystal structure of the obtained lutetium fluoride nanoparticles (space group Fd3m) were confirmed. It also has been shown that LuF<sub>3</sub> NPs have a size of ~ 200&#xa0;nm, PDI = 0.149 and ζ-potential of −28&#xa0;mV, confirming the colloidal stability of the nanoparticles’ sol. LuF<sub>3</sub> NPs accumulate in B16/F10 cells and exhibit a cytotoxic effect at concentrations of 2.32&#xa0;µg/mL and above. LuF<sub>3</sub> NPs demonstrate pH-dependent radiocatalytic activity, which is most expressed at pH = 6.5, corresponding to the tumor microenvironment. The radiocatalytic activity of LuF<sub>3</sub> NPs may cause their radiosensitizing effect on B16/F10 cells when exposed to X-rays. This effect is manifested in a decrease in the clonogenic activity of the cells and induction of cell death via apoptosis. The combined effect of X-ray radiation and LuF<sub>3</sub> NPs is synergistic (coefficient of interaction, CI &lt; 1), which confirms the effectiveness of this approach in radiotherapy of melanoma. The molecular mechanisms underlying this effect are hyperpolarization of mitochondrial membranes (1.6 times higher than the unirradiated control at a dose of 2&#xa0;Gy) and increase in the level of intracellular reactive oxygen species (1.5 times higher than the unirradiated control at a dose of 2&#xa0;Gy). The Dose Enhancement Factor (DEF) was quite high and ranged from 1.26 (2.32&#xa0;µg/mL at 2&#xa0;Gy) to 4.3 (23.2&#xa0;µg/mL at 4&#xa0;Gy). Thus, lutetium fluoride nanoparticles can become the basis for the development of advanced radiotherapy approaches aimed at increasing the effectiveness of radiotherapy by increasing the radiosensitivity of tumor cells.</p>

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Radiocatalytically active lutetium fluoride nanoparticles as a synergistic radiosensitizer against melanoma cells under X-ray irradiation

  • 期刊论文

  • 发表日期：

    2026年5月28日

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  • Darya A. Vinnik,
  • Nikita N. Chukavin,
  • Nikita A. Pivovarov,
  • Irina V. Savintseva,
  • Timur R. Nizamov,
  • Anton L. Popov

摘要

Melanoma is considered one of the most radioresistant types of cancer. Enhancing the therapeutic effect of ionizing radiation using nanoparticles is an advanced strategy for modern radiotherapy of solid tumors. This study presents the results of an analysis of the radiosensitizing effect of lutetium fluoride nanoparticles (LuF3 NPs) on a culture of B16/F10 melanoma cells exposed to X-rays. A comprehensive analysis of the physicochemical properties, intracellular accumulation, and cytotoxicity of LuF3 NPs was performed, as well as an assessment of their radiocatalytic activity and radiosensitizing effect in vitro. The elemental composition and crystal structure of the obtained lutetium fluoride nanoparticles (space group Fd3m) were confirmed. It also has been shown that LuF3 NPs have a size of ~ 200 nm, PDI = 0.149 and ζ-potential of −28 mV, confirming the colloidal stability of the nanoparticles’ sol. LuF3 NPs accumulate in B16/F10 cells and exhibit a cytotoxic effect at concentrations of 2.32 µg/mL and above. LuF3 NPs demonstrate pH-dependent radiocatalytic activity, which is most expressed at pH = 6.5, corresponding to the tumor microenvironment. The radiocatalytic activity of LuF3 NPs may cause their radiosensitizing effect on B16/F10 cells when exposed to X-rays. This effect is manifested in a decrease in the clonogenic activity of the cells and induction of cell death via apoptosis. The combined effect of X-ray radiation and LuF3 NPs is synergistic (coefficient of interaction, CI < 1), which confirms the effectiveness of this approach in radiotherapy of melanoma. The molecular mechanisms underlying this effect are hyperpolarization of mitochondrial membranes (1.6 times higher than the unirradiated control at a dose of 2 Gy) and increase in the level of intracellular reactive oxygen species (1.5 times higher than the unirradiated control at a dose of 2 Gy). The Dose Enhancement Factor (DEF) was quite high and ranged from 1.26 (2.32 µg/mL at 2 Gy) to 4.3 (23.2 µg/mL at 4 Gy). Thus, lutetium fluoride nanoparticles can become the basis for the development of advanced radiotherapy approaches aimed at increasing the effectiveness of radiotherapy by increasing the radiosensitivity of tumor cells.