Zeta potential and solubility to toxic ions as mechanisms of lung inflammation caused by metal/metal oxide nanoparticles

The toxicology of nanoparticles (NPs) is an area of intense investigation that would be greatly aided by improved understanding of the relationship between NP structure and inflammogenicity. To evaluate how their physicochemical parameters influence toxicity, we assembled a panel of 15 metal/metal oxide NPs and attempted to relate various physicochemical parameters, including zeta potential (¿P) and solubility, to lung inflammogenicity. The acute pulmonary inflammogenicity of the 15 NPs showed a significant correlation with one of two structural parameters-¿P under acid conditions for low-solubility NPs and solubility to toxic species for high-solubility NPs. ¿P is the electrical potential created between the surface of a particle, with its associated ions, and the medium it exists in and provides information concerning the particle surface charge. We suggest that inside the phagolysosome under acid conditions, a high positive ¿P may allow NPs to damage the integrity of the phagolysosomal membrane leading to inflammation. In the case of high-solubility NPs, inflammogenicity depends on the ions that are produced during dissolution of NP inside the acidic phagolysosomes; if the ions are toxic, then phagolysosomes will be destabilized and cause inflammation. These two parameters may have utility in preliminary assessment of the potential lung inflammation hazard of the large number of NPs that require testing.