Silica Nanoparticles Decorated with Ceria Quantum Dots Modulate Intra- and Extracellular Reactive Oxygen Species Formation and Selectively Reduce Human A375 Melanoma Cell Proliferation.

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