Rod-shaped iron oxide nanoparticles are more toxic than sphere-shaped nanoparticles to murine macrophage cells

Variable sizes of nanoparticles, ranging from nano to micro scale, are of toxicological interest. In the present study, the authors hypothesized that, in addition to the size, the shape of iron oxide (Fe2O3) nanoparticles is a major factor that contributes to particle cytotoxicity. Cytotoxicity to mouse macrophage cells (RAW 264.7) was investigated using 3 different particles: micro-sized Fe2 O3 (M-Fe2O3), nano-sized Fe2O3 (N-Fe2O3), and rod-shaped Fe2O3 (R-Fe2O3). Whereas M-Fe2O3 and N-Fe2O3 were located in the vacuole as aggregates, R-Fe2 O3 was often spread throughout the cytoplasm. The extent of cytotoxicity measured by the water soluble tetrazolium (WST-1) assay was in the order R-Fe2O3 ≈ N-Fe2O3 > M-Fe2O3, whereas the extent revealed by the lactate dehydrogenase assay was in the order R-Fe2O3 >> N-Fe2O3 ≈ M-Fe2 O3. In addition, the degree of tumor necrosis factor-α and reactive oxygen species (ROS) production was in the order of R-Fe2O3  > N-Fe2 O3 > M-Fe2O3. In addition, a much higher extent of necrosis was associated with the presence of R-Fe2O3. These results suggest that the higher degree of necrosis due to R-Fe2O3 is correlated with both the higher degree of membrane damage and ROS production by R-Fe2O3 compared with the results of the other Fe2O3 particles. These results also showed that the degree of cytotoxicity of nanoparticles should be evaluated based on shape as well as size, because changes in shape and size are accompanied by alterations in surface area, which relate closely to cytotoxicity.