Ein Schwerpunktprogramm der DFG


  • Professor Dr. Hans-Joachim Galla
    Institut für Biochemie
    Westfälische Wilhelms-Universität Münster
  • Professor Dr. C. James Kirkpatrick
    Institut für Pathologie
    Klinikum der Johannes-Gutenberg-Universität Mainz
  • Prof. Dr. Michael Maskos
    Institut für Physikalische Chemie
    Johannes Gutenberg-Universität Mainz
  • Professor Dr. Roland Stauber
    Hals-, Nasen-, Ohrenklinik und Poliklinik
    Klinikum der Johannes-Gutenberg-Universität Mainz
1 Phase 1: until Decembre 2010
2 Phase 2: since January 2011

Biological Influence of Nanoparticles on Exposed Epithelial Respiratory Surfaces.

The rapid expansion of nanotechnology has resulted in a vast array of nanoparticles (NPs), which are increasingly being used for commercial purposes and hence are increasingly released into our environment. The unusual physico-chemical properties of engineered NPs differ from those bulk materials of the same composition, allowing them to execute novel activities. However, the novel properties of NPs also raise concerns about adverse effects on biological systems, as some studies indicate that NPs could exert toxic effects and pose hazards to humans.1,2 In contrast to the extensive literature on the physicochemical properties of NP as well as on their potential novel applications, information about the fundamental biological cause-effect relationships remain fragmented. Progress is hampered by the lack of interdisciplinary approaches integrating physicochemical and bio-physical NP characterization together with the cellular reactions and the underlying molecular mechanisms, which are triggered by NP exposure.3 In contrast to animal studies for NP-toxicology, current nanobiology needs a consistent, accurate and biologically motivated approach for making comparisons of response using highly standardized and relevant in vitro systems across nanoparticle size and type.
The biological responses induced by NPs not only depend on particle physico-chemistry, but the effective „cellular dose" is also dependent on the properties of the particles themselves (e.g., size, density, surface chemistry), their solution (viscosity, density, presence of proteins, etc.) and the cellular target. Hence, to developing a deeper quantitative understanding of the cellular-level response to NPs, a vigorous physico-chemical characterization of NPs by standardized operating procedures (SOPs) together with SOP controlled cellular in vitro systems is of utmost importance.
As evidence for health risks of NP after inhalation has been increasing, the alveolar-capillary barrier is certainly one of the key targets of inhaled NPs leading to local or systemic effects. This cellular barrier from airspace to capillary blood, composed of alveolar epithelial and pulmonary capillary endothelial cells, is coated by the pulmonary surfactant, a thin lipid-protein film, which is the first barrier that NPs encounter in order to cross the phase boundaries. The large alveolar epithelial surface area is the subsequent prime target where NPs influence various biological processes. Biological responses may be stimulated directly by cellular entry of NPs (uptake via endocytosis or direct entry) or indirectly by NPs influencing various signal transduction pathways vital for proliferation, cell cycle control, apoptosis or differentiation. To date, mainly reactive oxygen species (ROS) have been described to be induced by the uptake of NPs, resulting in the activation of cellular stress response pathways. In contrast, neither the interactions of NPs with the pulmonary surfactant, intracellular organelles, the mitotic machinery and the chromosomes during cell division, nor the effects of NPs on global gene expression programs have been characterized systematically. Intriguingly, the majority of the biological effects reported for inhaled NPs resemble pathways detectable also in epithelial cancer.
In order to achieve a comprehensive understanding of the Biological Influence of Nanoparticles on Exposed Epithelial Respiratory Surfaces and its correlation with the physicochemical properties of NPs, leading experts on NP characterization, biophysics, particle toxicology and cell biology have joined forces. Our interdisciplinary consortium will apply state-of-the-art technologies for the production and characterization of NPs, their detection and measurement in biological systems, as well as the analysis of biological responses induced by defined NP formulations.