John Wiley & Sons, Ltd.

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

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Variable sizes of nanoparticles (NPs), ranging from nano to micro scale, have been of toxicological interest. We hypothesized that the shape as well as size of iron oxide (Fe2O3) NPs is one of the major factors contributing to particle cytotoxicity. Cytotoxicity to mouse macrophage cells (RAW 264.7) was investigated using three different particles: micro‐sized Fe2O3 (M‐Fe2O3), nano‐sized Fe2O3 (N‐Fe2O3), and rod‐shaped Fe2O3 (R‐Fe2O3). While M‐ 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 WST‐1 assay was in the order R‐Fe2O3 ~ N‐Fe2O3 > M‐Fe2O3, whereas the extent revealed by the LDH assay was in the order R‐Fe2O3 >> N‐Fe2O3 ~ M‐Fe2O3. In addition, the degree of TNF‐a and ROS production was in the order of R‐Fe2O3 > N‐Fe2O3 > M‐Fe2O3. We also found a much higher extent of necrosis to be 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 showed that the degree of cytotoxicity of nanoparticles should be evaluated based on shape as well as size, since changes in shape and size are accompanied by alterations in surface area which closely relate to cytotoxicity. Environ Toxicol Chem © 2014 SETAC

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