4.6 Article

X-ray sensitive selenium-containing Ru complexes sensitize nasopharyngeal carcinoma cells for radio/chemotherapy

Journal

JOURNAL OF MATERIALS CHEMISTRY B
Volume 11, Issue 24, Pages 5607-5618

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d3tb00064h

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In this study, a selenium-containing ruthenium complex (RuSe) was designed as a radiosensitizer to enhance the killing effect of radiotherapy on nasopharyngeal carcinoma cells. The results showed that RuSe, compared to RuC, could potentiate the lethality of radiotherapy by inducing ROS over-production, decreasing mitochondrial membrane potential, and arresting the cell cycle. Furthermore, RuSe was superior to RuC in inducing apoptotic cell death. This study demonstrates an effective and safe strategy for the application of RuSe complexes to cancer-targeted chemo/radiotherapy and sheds light on the potential mechanisms of selenium-containing drugs as radiotherapy sensitizers.
Radiotherapy has been extensively applied to cancer therapy in clinical trials. However, radiation resistance and dose limitation generally hamper the efficacy of radiotherapy. There is an urgent need for radiosensitizers with high efficiency and safety to enhance the anti-tumor effect of radiotherapy. In this paper, a selenium-containing (Se) ruthenium (Ru) complex (RuSe) was designed as a radiosensitizer to synergistically augment the killing effect of radiotherapy on nasopharyngeal carcinoma cells. In this system, the heavy atomic effect of Ru enhances the photoelectron production triggered by X-rays, thus inducing a burst of reactive oxygen species (ROS). In addition, Se atoms with a strong polarization property were introduced into the ligand of the metal complex to enhance the tumor chemo/radiotherapy effect. Consequently, RuC with a weak atomic polarization effect, as a comparison for RuSe, was also rationally explored to elucidate the role of Se atoms on chemo/radiotherapy sensitization. Indeed, compared with RuC, RuSe at a sub-toxic dose was able to potentiate the lethality of radiotherapy after preconditioning with cancer cells, by inducing ROS over-production, decreasing the mitochondrial membrane potential, and arresting the cell cycle at the sub-G1 phase. Furthermore, upon radiation, RuSe was superior to RuC, by inducing apoptotic cell death by activating caspase-3, -8, and -9. In summary, this study not only demonstrates an effective and safe strategy for the application of RuSe complexes to the cancer-targeted chemo/radiotherapy of human cancers, but also sheds light on the potential mechanisms of such Se-containing drugs as efficient radiotherapy sensitizers.

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