Molecular interactions of nanomaterials and organisms: defining biomarkers for toxicity and high-throughput screening using traditional and next-generation sequencing approaches.

The toxicity of nanomaterials depends on the basic interaction of the chemistry of the material with the molecular pathways in an organism. To design safe and sustainable nanomaterials, more detailed information on the molecular interaction and biochemical machinery that is altered in an organism upon contact with a nanomaterial is needed. There are a multitude of papers now on the toxicity of nanomaterials to various model organisms from human to ecological models, but many focus on acute high dose exposures and research on the toxicity of other chemicals has shown that the dose of a chemical can have a tremendous impact on the pathways that are affected within the organism. The most common pathways investigated in nanotoxicity experiments are related to oxidative stress, yet oxidative stress can be a temporary and natural response to an insult without a negative outcome. There are a multitude of other potential mechanisms that may be triggered in response to a toxin at sublethal exposures. Here we present a review documenting the evidence to date on the indicators of the molecular response to nanomaterials from in vitro and in vivo studies. Alternative pathways as indicated by single biomarker, global gene expression studies and next generation sequencing approaches are discussed as well as the impacts of nanomaterial type, dose, and the types of system studied. Specific mechanisms that are impacted by a nanomaterial can be used as the basis of better high-throughput methods for evaluating how nanomaterial chemistry impacts toxicity and support models to predict the toxicity of future nanomaterials.