Silica Nanoparticles\nDecorated with Ceria Quantum\nDots Modulate Intra- and Extracellular Reactive Oxygen Species Formation\nand Selectively Reduce Human A375 Melanoma Cell Proliferation

Nanomaterials show great promise for cancer treatment.\nNonetheless,\nmost nanomaterials lack selectivity for cancer cells, damaging healthy\nones. Cerium dioxide (ceria, CeO<sub>2</sub>) nanoparticles have been\nshown to exert selective toxicity toward cancer cells due to the redox\nmodulating properties they display as their size decreases. However,\nthese particles suffer from poor suspension stability. The efficacy\nof CeO<sub>2</sub> nanoparticles for cancer treatment is hampered\nby their innate high surface energy, which leads to particle agglomeration\nand, consequently, reactivity loss. This effect increases as particle\nsize decreases; as such, quantum dots (QDs) suffer most from this\nphenomenon. In this study, it is proposed that silicon dioxide (silica,\nSiO<sub>2</sub>) nanoparticles can provide an inert platform for surface\nencrusted CeO<sub>2</sub> QDs and that the resulting nanocomposite\n(hereafter <sup>QD</sup>CeO<sub>2</sub>/SiO<sub>2</sub>) not only\nwill exhibit negligible agglomeration compared with CeO<sub>2</sub> alone but also will improve the modulation of reactive oxygen species\n(ROS) leading to selective reduction of human A375 melanoma cell proliferation.\nThe SiO<sub>2</sub> nanoparticles had a bimodal size distribution\nwith median particle size of 66 and 168 nm, while the CeO<sub>2</sub> quantum dots encrusted on their surface had a size of 3.2 nm. An\nelevated Ce<sup>3+</sup>/Ce<sup>4+</sup> ratio led to the <sup>QD</sup>CeO<sub>2</sub>/SiO<sub>2</sub> nanocomposite displaying synergistic\nsuperoxide dismutase- and catalase-like activity, favoring the accumulation\nof ROS at pH 6.5 which translated into <sup>QD</sup>CeO<sub>2</sub>/SiO<sub>2</sub> exerting selective oxidative stress in, and toward,\nthe melanoma cells. Treatment with 50 μg mL<sup>–1</sup> <sup>QD</sup>CeO<sub>2</sub>/SiO<sub>2</sub> significantly reduced\ncell proliferation by 27% compared to untreated control cells in the\ncolony formation assay. Treatment with either SiO<sub>2</sub> or CeO<sub>2</sub> alone did not affect the cell proliferation. These results\nhighlight the benefit of dispersing CeO<sub>2</sub> QDs on the surface\nof core nanoparticles and the resulting enhancement of selective redox\nreactivity and proliferation arrest when compared to CeO<sub>2</sub> nanoparticles alone. Furthermore, the method employed here to encrust\nCeO<sub>2</sub> QDs could lead to the facile synthesis of new nanocomposites\nwith enhanced control of ROS activity, not only for <i>in vitro</i> studies using other cancer cell lines of interest but also in animal\nmodels and perhaps leading to clinical trials in melanoma patients.