Copper (Cu) and Copper oxide (CuO) particles induce a cytotoxic response due to their release of copper ions.


Studies of Cu and CuO particles have shown that these particles as others too tend to agglomerate quickly in cell culture medium. These agglomerates were taken up by different cell types in vesicular structures mostly and were not described to be free in the intracellular fluid (cytosol).

Cu and CuO nanoparticles as long as they are not coated are soluble in aqueous suspensions and release copper ions [1,2]. Among the dose dependent cytotoxic effects, observed between 1-80 µg/ml [1,2,3,4] a gene expression study could demonstrate after treatment of A549 human lung carcinoma cells with 25 µg/ml CuO nanoparticles (300 nm agglomerates of 50 nm primary particle size) an up-regulation of metabolic processes and stress response genes as well as the down regulation of specific cellular processes and cell cycle regulating genes [5]. In parallel the supernatant of CuO nanoparticles incubated cell culture medium was used for treatment experiments too and most of the effects observed with CuO nanoparticles could be seen as well, indicating that the CuO-NP toxicity is mainly due to the Cu ion release [1,2,3,4,5,6].


In comparison with other nano-sized metal oxides such as TiO2, ZnO, Fe3O4, Fe2O3 or carbon-based materials e.g. carbon nanotubes, the non-coated nano-sized copper or copper oxide particles induced always the most severe cytotoxic effects at similar concentrations [3,4].

Several studies compared micro-sized with nano-sized CuO and showed independent of the cellular systems used e.g. A549 [2,4], Hela or Chinese hamster oocytes [1], or CaCo-2 cells [6] that the nano-sized material induces more severe effects in these cells due to their higher release of Cu ions.



Literature arrow down

  • Studer, AM et al. (2010), Toxicol Lett, 197(3): 169-174.
  • Midander, K et al. (2009), Small, 5(3): 389-399.
  • Karlsson, HL et al. (2009), Toxicol Lett, 188(2): 112-118.
  • Karlsson, HL et al. (2008), Chem Res Toxicol, 21(9): 1726-1732.
  • Hanagata, N et al. (2011), ACS Nano, 5(12): 9326-9338.
  • Piret, JP et al. (2012), Nanotoxicology, 6(7): 789-803.


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