From a toxicology perspective, nanoparticles possess two features that promote their toxicity. The first involves physical-chemical characteristics, including particle surface area. The second is the ability of the nanoparticle to traverse cell membranes. These two characteristics are influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate in suspension, making it difficult to accurately deliver them for in vivo or in vitro experiments. Thus, we hypothesize that the nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. The proposed questions of this study are of great importance to the nanotechnology/toxicology community, namely the highly debated question of whether nanoparticle dispersion status (pre-exposure) is of importance. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (PBS, dispersion medium (DM), Survanta, or Pluronics). At each respective dose, well-dispersed and poorly dispersed (suspensions were sonicated utilizing a Branson Sonifer 450, 25W continuous output, 20 min or 5 min, respectively) suspensions were created. Mice (male, C57BL/6J, 7 weeks old) were given 0-80 mg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 & 7 days post-exposure, mice underwent whole lung lavage (WLL) to assess pulmonary inflammation and injury as a function of dispersion status, dose, and time. Results show that pre-exposure dispersion status correlates with particle bioactivity. In fact, the particle/media combination that produced the smallest hydrodynamic particle size (nano-NiO2 suspended in DM & sonicated for 20 min. = 7.5 nm) produced a greater increase in PMNs, LDH activity, as well as albumin levels in WLL fluid than the other nano-nickel/suspension media combinations. These results indicate that a greater degree of pre-exposure dispersion increases particle bioactivity/toxicity in the lung.
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona