Tissue distribution following 28 day repeated oral administration of aluminum-based nanoparticles with different properties and the in vitro toxicity

Abstract

The tissue distribution and toxicity of nanoparticles (NPs) depend on their physical and chemical properties both in the manufactured condition and within the biological system. We characterized three types of commercially available aluminum-based NPs (Al-NPs), two rod-type aluminum oxide NPs (Al2O3, AlONPs), with different aspect ratios (short [S]- and long [L]-AlONPs), and spherical aluminum cerium oxide NPs (AlCeO3, AlCeONPs). The surface area was in order of the S-AlONPs > L-AlONPs > AlCeONPs. Very importantly, we found that AlCeONPs is Al2O3-coated CeO2 NPs, but not AlCeO3 NPs, and that the Al level in AlCeONPs is approximately 20% of those in S- and L-AlONPs. All three types of Al-NPs were slightly ionized in gastric fluid and rapidly particlized in the intestinal fluid. There were no significant differences in the body weight gain following 28days of repeated oral administration of the three different types of Al-NPs. All Al-NPs elevated Al level in the heart, spleen, kidney and blood at 24hours after the final dose, accompanied by the altered tissue level of redox reaction-related trace elements. Subsequently, in four types of cells derived from the organs which Al-NPs are accumulated, H9C2 (heart), HEK-293 (kidney), splenocytes and RAW264.7 (blood), S-AlONPs showed a very low uptake level and did not exert significant cytotoxicity. Meanwhile, cytotoxicity and uptake level were the most remarkable in cells treated with AlCeONPs. In conclusion, we suggest that the physicochemical properties of NPs should be examined in detail before the release into the market to prevent unexpected adverse health effects. In the present study, we investigated tissue distribution following 28 -days of repeated oral administration and in vitro toxicity of three types of commercially available aluminum-based nanoparticles (Al-NPs), two rod-type aluminum oxide nanoparticles (Al2O3, AlONPs), with different aspect ratios (short (S)- and long (L)-AlONPs), and spherical aluminum cerium oxide nanoparticles (AlCeO3, AlCeONPs). Based on results from this study, we suggest that AlCeONPs are Al2O3-coated CeO2 NPs, but not AlCeO3 NPs, and that AlCeONPs may accumulate more and show higher toxicity than S- and L-AlONPs. In addition, the physicochemical properties of NPs should be examined in detail the release into the market to prevent unexpected adverse health effects