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 Fe₂O₃ (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-Fe₂O₃ 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-Fe₂O₃. In addition, the degree of tumor necrosis factor-α and reactive oxygen species (ROS) production was in the order of R-Fe₂O₃>N-Fe₂O₃>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.