Nano “Trojan Horse” Study Gets Top Billing

Cal Baier-Anderson, Ph.D., is a Health Scientist.

Each year, the journal Environmental Science & Technology selects a list of Top Papers it has published that are “expected to have a significant and long-lasting impact on the field.” For 2007, its choice for the top environmental science paper addresses a curious facet of the behavior of certain metal oxide nanoparticles:  They can behave as “Trojan horses,” getting inside cultured lung cells and causing significant damage.

The paper, “Exposure of Engineered Nanoparticles to Human Lung Epithelial Cells: Influence of Chemical Composition and Catalytic Activity on Oxidative Stress,” demonstrates that when lung epithelial cells – the type that line the lungs – are exposed in culture to various forms of metal oxides, they readily take them up if they are in the form of nanoparticles, but not if they’re dissolved or in the form of larger particles.  Once inside the cells, the metals generate reactive oxygen species, such as hydrogen peroxide, which can cause a type of damage called oxidative stress.

The authors liken this uptake-and-damage mechanism to that of the Trojan horse:  The nanoparticles appear to “trick” the cells to let them in, and once inside, the toxic metals can wreak havoc.  Have a look at the nifty picture in the accompanying story announcing ES&T’s selection of this paper.  By gaining access to the inside of the cell via nanoparticle transport, metal-generated reactive oxygen species reach critical intracellular targets where they can do damage.

This well-designed study further demonstrates that, while the nano forms of all of the tested metal oxides are preferentially taken up into cultured cells, they differ in their ability to cause oxidative stress.  For example, metal oxide nanoparticles containing cobalt and manganese are much more potent triggers of oxidative stress than those containing iron or titanium.

The major limitation of this study is that it was performed in cell cultures, not in whole animals.  While useful for uncovering mechanisms of toxicity and developing hypotheses for further testing, such in vitro tests do not always perfectly mimic what happens in vivo.  It remains to be seen, therefore, whether the observed effects are also seen in a whole animal study.

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  1. Steven Fowkes
    Posted March 8, 2008 at 10:17 am | Permalink

    Was a oxidative-damage comparison made with an equimolar exposure of the metal oxide as a simple salt?

  2. Cal Baier-Anderson
    Posted March 10, 2008 at 6:18 am | Permalink

    Good question!

    Yes, equimolar amounts of metals were tested. According to the supporting information provided by the authors on the ES&T website (subscription required), the following concentrations were tested, noting that since there are no known titania salts soluble in neutral, aqueous media, titanium was not tested in this component of the study:

    FeCl3 was tested at 0.371 mM, corresponding to 30 ppm Fe2O3,
    MnCl2 was tested at 0.393 mM, corresponding to 30 ppm Mn3O4, and
    CoCl2 was tested at 0.374 mM, corresponding to 30 ppm Co3O4.