Cellular Toxicity of Nanostructures

New technologies are going to explore the creation of functional devices at nanometer scales, which necessitates the production and handling of components of submicron size, very often in large quantities. The last decade has seen the rapid development of various nanostructures, especially that of carbon nanotubes (CNTs). Due to the many exceptional properties, CNTs are foreseen to be the building blocks of new technologies and are highly desirable in many industrial products such as flat panel screens, composite materials, catalysis supports, sensors, just to mention a few. But CNTs are not the only nanostructures in the incredible progression of production of nanosized objects. Here below are few examples:

Figure a. shows the filaments of asbestos, The health hazard of the new nanofilaments, CNTs (b), TiO2 (c) and BNNts (d) is related to the structural ressemblance to asbestos, which is know to cause lung cancer. (The scale, from left to right: 50 µm, 100 nm, 50 nm and 5 µm).

Although these and other nanostructures (inorganic nanofilaments (INFs): nanowires, nanotubes) are very promising, the putative health hazards associated with their production and handling has not been properly addressed in the past. A special fear is related to their ressemblance to asbestos, which causes lung cancer.

In collaboration with the group of Prof. Beat Schwaller at the Department of Anatomy of the University of Fribourg, we are studying the acute cellular toxicity of various nanostructures including Carbon-Based Nanomaterials [1], TiO2-based Nanofilaments [2], Boron Nitride nanowires, graphene etc.

The effect on the cell proliferation and cytotoxicity of the nanostructures are evaluated by several assay like FMCA, DNA or MTT combined with direct cell counting methods while potential cell morphological alterations are examined by cytopathological observations.An example is given below for macrophages (RAW 264.7) exposed to BNNTs for 5 days with variable concentration.

Cythopathological observations of epithelial cells exposed to nanostructures showing several cell alterations.

The effect of nanomaterials on macrophages RAW264.7 determined by DNA assays. Measurements were performed after 5 days of exposure to 0.2, 2, and 20 μg/mL BNNTs dispersed in 20 μg/mL Tween 80. Cells were treated with pristine (p-CNTs), functionalized (f-CNTs), carbon nanotubes and BNNTs. (The value for untreated control cells was defined as 100%.)

The cell proliferation varies strongly with the type of nanostructure, its surface state (functionalized or pristine), on the surface defects and on the tortuosity of the nanofilaments. We are seeking for further parameters which influence cell viability and which on long exposure could cause a severe disease.

[1] Magrez, A., et al., Cellular toxicity of Carbon-Based Nanomaterials. Nano Lett, 2006. 1121-1125.
[2] Magrez, A., et al., Cellular toxicity of TiO2-based nanofilaments. ACS Nano, 2009. 3(8): p. 2274-80.
[3] Horvath, L., et al., In Vitro Investigation of the Cellular Toxicity of Boron Nitride Nanotubes. ACS Nano, 2011. 5(5) p. 3800-3810.
[4] Horvath, L., et al., Cell type Dependence of Carbon based Nanomaterial Toxicity. Physica Status Solidi B, 2010. 247(11/12): p. 3059–3062.
[5] Horváth L., Magrez A., Schwaller B., Forró L. Toxicity Study of Nanofibers, in Supramolecular Structure and Function 10, 2011, Springer Netherlands