The chemistry of pure cerium oxide (CeO_2-x) nanoparticles has been widely studied since the 1970s, especially for chemical catalysis. CeO_2-x nanoparticles have been included in an important class of industrial metal oxide nanoparticles and have been attributed a range of wide applications, such as ultraviolet absorbers, gas sensors, polishing agents, cosmetics, consumer products, high-tech devices and fuel cell conductors. Despite these early applications in the field of chemistry, the biological effects of CeO_2-x nanoparticles were only explored in the 2000s. Since then, CeO_2-x nanoparticles have gained a spot in research related to various diseases, especially the ones in which oxidative stress plays a part. Due to an innate oxidation state variation on their surface, CeO_2-x nanoparticles have exhibited redox activities in diseases, such as cancer, acting either as an oxidizing agent, or as an antioxidant. In biological models, CeO_2-x nanoparticles have been shown to modulate cancer cell viability and, more recently, cell death pathways. However, a deeper understanding on how the chemical structure of CeO_2-x nanoparticles (including nanoparticle size, shape, suspension, agglomeration in the medium used, pH of the medium, type of synthesis and crystallite size) influences the cellular effects observed remains to be elucidated. In the present review, the chemistry of CeO_2-x nanoparticles and their impact on biological models and modulation of cell signalling, particularly focusing on oxidative and cell death pathways, were investigated. The deeper understanding of the chemical activity of CeO_2-x nanoparticles may provide the rationale for further biomedical applications towards disease treatment and drug delivery purposes.

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