Toxicogenomics to Improve Comprehension of the Mechanisms Underlying Responses of In Vitro and In Vivo Systems to Nanomaterials: A Review

Abstract

Engineered nanomaterials are commonly defined as materials with at least one dimension of 100 nanometers or less. Such materials typically possess nanostructure-dependent properties (e.g., chemical, mechanical, electrical, optical, magnetic, biological), which make them desiderable for commercial or medical application. However, these same properties may potentially lead to nanostructure-dependent biological activity that differs from and is not directly predicted by the bulk properties of the constitutive chemicals and compounds. Nanoparticles and nanomaterials can be on the same scale of living cells components, including proteins, nucleic acids, lipids and cellular organelles. When considering nanoparticles it must be asked how man-made nanostructures can interact with or influence biological systems. Carbon nanotubes (CNTs) are an example of carbon-based nanomaterial, which has won a huge spreading in nanotechnology. The incorporation of CNTs in living systems has raised many concerns because of their hydrophobicity and tendency to aggregate and accumulate into cells, organs, and tissues with dangerous effects.Applications of toxicogenomics to both investigative and predictive toxicology will contribute to the in-depth investigation of molecular mechanisms or the mode of nanomaterials action that is achieved by using conventional toxicological approaches. Parallel toxicogenomic technologies will promote a valuable platform for the development of biomarkers, in order to predict possible nanomaterial's toxicity. The potential of characteristic gene expression profiles ("fingerprint") of exposure or toxicological response to nanoparticles will be discussed in the review to enhance comprehension of the molecular mechanism of in vivo and in vitro system exposed to nanomaterials.

One low-dose exposure of gold nanoparticles induces long-term changes in human cells

“…Others have found low doses of Au NPs to alter cell migration and proliferation, stem cell differentiation, and membrane receptor internalization (13)(14)(15)(16). Many chemicals that trigger changes to cellular signaling pathways and induce molecular responses elicit no acute toxicological response (17). Therefore, a more nuanced description of NP effects beyond "toxic" or "not toxic" is needed.…”

Edible Bio-Based Nanostructures: Delivery, Absorption and Potential Toxicity

“…The exact determination of these effects still remains to be clearly identified, although intrinsic physicochemical characteristics of bio-based nanostructures such as size, surface nature and dispersion state (aggregation or agglomerated) seem to be of outmost importance. A tool that could contribute to the explanation of nanostructures' modes of action and potential nanotoxicity would be the use of toxicogenomics in combination with traditional approaches and other-omic technologies (i.e., proteomics and metabolomics) [2,125]. In particular, systems biology technology has been developed to integrate all information at mRNA, protein and metabolite levels.…”

“…This can generate pathway information and provide the capacity to measure subtle perturbations of pathways caused by nanostructures [132]. For instance, the measurement of the pattern of gene expression levels upon exposure to nanostructures can provide useful information about the mechanism of action of bio-based nanostructures [125]. Therefore, it is fundamental to understand the complex in vitro, in vivo and in silico biological systems data integration and computational modeling.…”

Toxicogenomics of iron oxide nanoparticles in the nematodeC. elegans

“…(Soenen et al, 2011) Transcriptomic studies can help to elucidate the molecular mechanisms involved in NP response and pinpoint key genes able to predict the toxicity or the genetic susceptibility to different NP properties. (Nuwaysir et al, 1999, Aardema and MacGregor, 2002, Poma and Di Giorgio, 2008 This research field, coined nanotoxicogenomics, will further our understanding on nanotoxicity mechanisms. (Tino et al, 2014) High-throughput approaches like microarrays or next generation sequencing can be combined with 'gene by gene' techniques, mainly qPCR, which are highly quantitative and sensitive to interrogate a relatively small number of transcripts in a larger set of samples.…”

“…However, these mechanistic cues should be confirmed by post-hoc A c c e p t e d M a n u s c r i p t histological analysis or specific genetic experiments to test the importance and significance of the pathways identified. (Poma and Di Giorgio, 2008, Elingarami et al, 2013, Tino et al, 2014 Nanotoxicogenomic studies can be performed in nanoparticle-treated cells, simple invertebrates (Poynton et al, 2012, Starnes et al, 2016 or more complex vertebrates (Truong et al, 2013, Teeguarden et al, 2014. Invertebrate models share many biological traits with…”