Institute of Energy and Environmental Technology (IUTA), Germany; University of Gdansk, Poland;
Metal nanoparticles(M-NPs) are among the most widely used types of manufactured nanomaterials. Interactions between M-NPs and biological systems are thus inevitable. At present, there are many gaps in the understanding of how M-NPs interact with the biological systems, behave inside cells and modify cellular biochemistry and function.
The biological barriers constitute a first line of defence against foreign material and xenobiotics, thus are expected targets of NPs. On the other hand, M-NPs are expected to be successfully applied as delivery platforms for increasing drug transport across barriers. It is therefore of paramount importance to characterize the impact of this class of NPs on barrier function as its impairment can seriously compromise normal physiology leading to disease.
NanoBarriers primary goal is to provide missing critical information about the effects of M-NPs by clarifying the mechanisms underlying the cellular and molecular effects of M-NPs of industrial, biomedical and consumer interest(TiO2, SiO2, Ag and Au) on in vitro models of intestinal and placental barriers. The present project will investigate not only their toxicological potential but also the impact of low, non-cytotoxic and likely more realistic concentrations of the M-NPs on cell barrier physiology. A variety of toxicity endpoints will be evaluated such as cellular morphology, metabolism, mitochondrial function and immunotoxicity. An innovative approach to evaluate the impact of M-NPs on cell barrier physiology will be employed. To our knowledge, this is the first attempt to investigate the effects of exposure to M-NPs on transepithelial resistance, ion homeostasis and regulation of intracellular pH and cell volume, important aspects of cell barrier physiology. The expression and activity of pivotal transporters will be determined by combining molecular, fluorescence and electrophysiological techniques. This functional approach will give a quantitative insight whether this type of NPs can compromise the barrier function and interfere with ion transport across the cell. In silico studies will enable to correlate the M-NPs physicochemical characteristics with the toxicological and biological effects induced by them in each biological barrier. Joint consideration of the physicochemical and biological properties is expected to allow grouping of the M-NPs and subsequent read-across that will be verified experimentally.
The studies will be to be developed by three partners with complementary expertise in the physicochemical (IUTA,Germany), biological(ISPUP) and computational(UGPL, Poland) domain.
NanoBioBarriers will provide new insights and a better comprehension of the relationship between phys-chem properties and the mechanisms involved in cell barrier responses to M-NPs. This knowledge is expected to contribute to support a comprehensive review of nanomaterials regulation but also to assist in the design of safer M-NPs, with obvious benefits for the human health.
Funding approved by the Competitiveness and Internationalization Operational Program in its FEDER component, by the Foundation for Science and Technology, I.P.
