Toxicological Effects of Cerium Oxide Nanoparticles in Biomedicine and Environmental Systems

The unique redox properties of cerium oxide nanoparticles (CeO2 NPs) have driven their adoption in diverse biomedical and industrial applications, ranging from antioxidant therapies to fuel additives. However, their small size and high surface reactivity confer the potential for unintended adverse interactions in biological and ecological contexts. In mammalian systems, inhalation or systemic administration of CeO2 NPs has been associated with oxidative stress, inflammation, DNA damage and apoptotic cell death in pulmonary, hepatic and renal tissues. This is mediated by overproduction of reactive oxygen species and depletion of endogenous antioxidants, leading to lipid peroxidation, up-regulation of pro-inflammatory cytokines and activation of cell-death pathways. In vitro studies in lung epithelial and hepatic cell lines corroborate these mechanisms, demonstrating mitochondrial dysfunction, genotoxic lesions and caspase-dependent apoptosis at clinically relevant concentrations. In environmental compartments, release of CeO2 NPs into aquatic ecosystems results in bioavailability to a wide range of organisms. In filter-feeding invertebrates such as Daphnia species, nCeO2 aggregates adhere to external surfaces and are ingested, causing alterations in swimming performance, survival and expression of detoxification enzymes. At the molecular level, exposure can induce differential regulation of xenobiotic-metabolising enzymes, including cytochromes P450, impacting detoxification capacity and developmental endpoints. At the ecosystem scale, the persistence and trophic transfer potential of CeO2 NPs raise concerns regarding bioaccumulation and long-term ecological disruption. Emerging evidence also highlights interactions between CeO2 NPs and co-contaminants or mixed nanoparticle formulations, which can exacerbate toxic outcomes through synergistic oxidative and inflammatory responses. A comprehensive understanding of exposure pathways, dose metrics (mass, surface area, number) and physicochemical transformations is therefore essential to inform safe design, regulatory thresholds and risk-mitigation strategies in both clinical and environmental settings.

Research from Nature Portfolio

Recent studies have demonstrated that combined administration of cerium oxide and zinc oxide nanoparticles in rodent models intensifies hepatic and renal oxidative injury and inflammatory responses beyond levels induced by single‐particle exposure. This composite formulation raises lipid peroxidation markers and pro-inflammatory cytokines, while histopathology reveals pronounced hepatocellular necrosis and renal parenchymal haemorrhage. These findings underscore the need to evaluate nanoparticle mixtures, as composite exposures may potentiate organ toxicity through additive or synergistic oxidative stress pathways.

Toxicological Effects of Cerium Oxide Nanoparticles in Biomedicine and Environmental Systems publication trend

The graph below shows the total number of articles in toxicological effects of cerium oxide nanoparticles in biomedicine and environmental systems across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive Oxygen Species (ROS): Highly reactive molecules containing oxygen that can damage cellular components. Bronchoalveolar Lavage Fluid (BALF): Fluid collected from the lung airways used to assess pulmonary inflammation. Genotoxicity: The capacity of agents to damage genetic information within a cell, causing mutations. Cytochrome P450 (CYP) Enzymes: A family of enzymes involved in the metabolism and detoxification of foreign compounds. Agglomeration: The clustering of nanoparticles into larger aggregates, affecting bioavailability and toxicity. Oxidative Stress: A cellular state resulting from an imbalance between ROS production and antioxidant defence.

References

1. Characterization and Expression of the Cytochrome P450 Genes in Daphnia magna Exposed to Cerium Oxide Nanoparticles. International Journal of Molecular Sciences (2024).
2. Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation. Scientific Reports (2023).
3. Behavior and Potential Impacts of Metal-Based Engineered Nanoparticles in Aquatic Environments. Nanomaterials (2017).
4. Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro. International Journal of Molecular Sciences (2013).
5. Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats. Particle and Fibre Toxicology (2017).
6. Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice. Oxidative Medicine and Cellular Longevity (2017).
7. Exposure to Cerium Dioxide Nanoparticles Differently Affect Swimming Performance and Survival in Two Daphnid Species. PLOS ONE (2013).