Xenopus as a model organism for testing nanoparticle toxicity

The novel chemical and physical properties of materials at the nanoscale have enabled practical and theoretical solutions to many pressing global problems, such as adequate supplies of clean water and energy.  However, little is known about the impact of these materials on the biosphere and, in particular, human health.  Titanium dioxide nanoparticles (TiO₂ NPs) are a common additive to food and other personal care products, and it is estimated that an American adult is exposed to more than 1 mg of Ti per kilogram body weight per day.  Thus, there is an immediate need for a comprehensive strategy to evaluate the potential toxicity of nanoparticles found in consumer products and to rapidly communicate the results to the scientific and medical communities.

Xenopus laevis, an aquatic frog, has been used for over a century by biologists as a model organism for studying development.  Embryos rapidly develop outside the mother, so that all stages of development can be easily observed under a light microscope.  Moreover, the large size of the egg (exceeding 1 mm) allows for direct injection of known amounts of material into the cell.  This circumvents questions about uptake that complicate the analysis of nearly all nanoparticles.  Investigators in the Huber lab have determined that sublethal doses of TiO₂ NPs have teratogenic effects that we have traced to a failure to maintain cell-cell contacts and a failure of the mesenchymal–epithelial transition (MET) during gastrulation, due to perturbations in the expression of ephrinA1 ligand.  The MET is believed to promote distal metastases, allowing cancer cells to regain epithelial properties and integrate into distant organs.  The power of using Xenopus as a model organism is that perturbations in development caused by NPs can be easily studied at the molecular level.