Uptake, biodistribution and translocation of nanomaterials in tissues and cells (NanoSolutions)
Biological Foundation for the Safety Classification of Engineered Nanomaterials (ENM): Systems Biology Approaches to Understand Interactions of ENM with Living Organisms and the Environment (NANOSOLUTIONS)
Launched in April 2013. Duration 4 years
The project NANOSOLUTIONS is supported by European Commission in the framework of FP7 Theme-NMP.2012.1.3-1 (Nanosciences, Nanotechnologies, Materials and New Product Technologies).
Grant Agreement Number: 309329.
The main objective of this research proposal is to identify and elaborate those characteristics of ENM that determine their biological hazard potential. This potential includes the ability of ENM to induce damage at the cellular, tissue, or organism levels by interacting with cellular structures leading to impairment of key cellular functions. These adverse effects may be mediated by ENM-induced alterations in gene expression and translation, but may involve also epigenetic transformation of genetic functions. We believe that it will be possible to create a set of biomarkers of ENM toxicity that are relevant in assessing and predicting the safety and toxicity of ENM across species. The ENM-organism interaction is complex and depends, not simply on the composition of ENM core, but particularly on its physico-chemical properties. In fact, important physico-chemical properties are largely governed by their surface properties. All of these factors determine the binding of different biomolecules on the surface of the ENM, the formation of a corona around the ENM core. Thus, any positive or negative biological effect of ENM in organisms may be dynamically modulated by the bio-molecule corona associated with or substituted into the ENM surface rather than the ENM on its own. The bio-molecule corona of seemingly identical ENM cores may undergo dynamic changes during their passage through different biological compartments; in other words, their biological effects are governed by this complex surface chemistry. We propose that understanding the fundamental characteristics of ENM underpinning their biological effects will provide a sound foundation with which to classify ENM according to their safety. Therefore, the overarching objective of this research is to provide a means to develop a safety classification of ENM based on an understanding of their interactions with living organisms at the molecular, cellular, and organism levels based on their material characteristics.
The project NANOSOLUTIONS is carried out by a consortium of 35 partners comprising research institutes and universities as well as industrial partners. The Leipzig group is involved in the work package „Translocation“and focuses on understanding the uptake mechanisms, biological fate and biodistribution of ENMs, which is fundamental to comprehend their possible toxicological endpoints. The objective of this WP is to study the translocation of ENMs across different barriers at cellular, tissue, organ and organism level as a function of their physico-chemical properties for a set of ENMs.
Specific objectives are:
- Study of uptake, biodistribution and biokinetics of ENMs at cellular and organism level
- Study the interaction of ENMs with endothelial barriers
- Understand the role of the biological corona around ENMs for uptake and translocation both „in vivo“ and „in vitro“.
Examples of imaging at cellular level with Ion Beam Microscopy (IBM) and Confocal Raman Microspectroscopy (CRM)
Fig. 1 Detection and quantification of NM in A549 cells. IBM elemental mapping of cells exposed to Al203, Fe2O3, TiO3, ZnO and CeO2 NMs at concentrations 30 µg/ml for 72 h. The top images provide the sulfur distribution as the protein marker for the cell.
| treated | 17900 ppm | 470 ppm | 4000 ppm | 11400 ppm | 12000 ppm |
| control | 58 ppm | 190 ppm |
Fig. 2 Raman mapping of different cell components together with CeO2 NMs in an A549 cell exposed to 30 µg/ml CeO2 NMs for 48 h. The image at the top represents the overlay of the 4 different cell components, nucleus, cytoplasm, lamellar bodies and cell.
