Toxicological Impacts of Zinc Oxide Nanoparticles

The widespread use of zinc oxide nanoparticles (ZnO NPs) across industrial, cosmetic and agricultural sectors has prompted extensive investigation into their interactions with living systems. Toxicity arises chiefly from partial dissolution of the particles under acidic or intracellular conditions, releasing zinc ions that drive oxidative stress and inflammatory pathways. Inhalation leads to local respiratory irritation, while systemic distribution via oral or parenteral routes results in accumulation in liver, spleen, kidney and brain. At the cellular level, ZnO NPs can compromise mitochondrial and lysosomal integrity, generate reactive oxygen species, trigger lipid peroxidation and activate regulated cell-death programmes such as apoptosis and ferroptosis. Factors such as particle size, surface coating and solubility modulate dissolution kinetics but often yield similar toxicokinetic profiles dominated by ionic zinc. Biological variables, including age and pre-existing conditions, further influence susceptibility, with older individuals showing heightened neuroinflammation and cognitive impairment. A comprehensive understanding of these mechanisms is essential for accurate risk assessment and the design of safer nano-enabled materials.

Research from Nature Portfolio

Recent animal studies have demonstrated that systemic exposure to ZnO NPs induces synergistic neurotoxicity in aged subjects. In both adult and old mice, intraperitoneal administration led to elevated pro-inflammatory cytokines in serum and brain, accompanied by increased oxidative stress and hippocampal pathology. An interaction between ageing and nanoparticle challenge resulted in marked deficits in learning and memory, underpinned by downregulation of the cAMP/CREB signalling cascade. These findings highlight a mechanistic link between ZnO NP exposure, neuroinflammation and cognitive decline in vulnerable populations.

Toxicological Impacts of Zinc Oxide Nanoparticles publication trend

The graph below shows the total number of articles in toxicological impacts of zinc oxide nanoparticles across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can oxidise and damage lipids, proteins and nucleic acids.

Ferroptosis: A regulated form of cell death driven by iron-dependent lipid peroxidation and characterised by mitochondrial shrinkage and membrane rupture.

cAMP/CREB signalling pathway: An intracellular cascade where cyclic adenosine monophosphate activates the cAMP response element-binding protein to regulate transcription of survival and plasticity genes.

References

1. ZnO NPs induce miR-342-5p mediated ferroptosis of spermatocytes through the NF-κB pathway in mice. Journal of Nanobiotechnology (2024).
2. Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms. Particle and Fibre Toxicology (2024).
3. Neurotoxicity induced by zinc oxide nanoparticles: age-related differences and interaction. Scientific Reports (2015).
4. Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice. PLOS ONE (2016).
5. Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes. Particle and Fibre Toxicology (2011).