The effect of different engineered nanomaterials (ENMs) on DNA damage and repair pathways
Engineered nanomaterials (ENMs) possess unique biological, physical and chemical properties due to their small size and high surface-area-to-volume-ratio. This makes these novel nano-sized materials particularly interesting for a very broad range of applications. Thus, the field of nanotechnology has undergone an enormous development in the last decades. However, the tremendous increase in production and utilization of various ENMs in consumer products and biomedical applications has led to growing concerns on potential unfavorable effects of ENM exposure to humans and the environment. While some studies demonstrated the absence of any ENM-dependent effects, adverse effects ascribed to the presence of ENMs have been reported for microorganisms, animals and human cells. Due to the enormous spectra of materials with diverse physico-chemical characteristics, the complexity of environmental and biological systems and the poor comparability of performed in vitro and in vivo studies, interpretation and generalization of these data remain a challenge. Nevertheless, for regulatory purposes, to prevent potential harm arising from future ENM application, but also to profit from the beneficial properties of ENM e.g. in prospective applications in clinical settings, detailed information on potential nanotoxicity is required. Since damage to the genetic material can lead to induction or promotion of carcinogenesis the DNA damaging potential of ENMs is of particular importance. Even though literature on nanomaterial genotoxicity grew over the past years, published data is still quite often inconclusive or controversial. Consequently, further clarification on potential ENM genotoxicity through reliable and robust toxicological in vitro and in vivo studies is still required. Providing this knowledge is a necessity for the future development of safe and effective nano-based biomedical applications.
This thesis aims to explore and characterize the genotoxic mechanism of industrially and medically relevant ENMs and to correlate their physico-chemical properties to a biological response. For this reason, a panel of different ENMs with highly varying chemical composition, size and functionalization was chosen for an initial genotoxicity screening, which was followed by an in-depth analysis of selected ENMs. Analyzed materials include graphene oxide (GO) as novel 2D-material, two types of multi-walled carbon nanotubes (MWNTs) as fiber-like structures, spherical particles such as amine-modified positively charged polystyrene nanoparticle (PS-NP) and three gold nanoparticles (Au-NPs) with a primary core size of 2-4 nm and different surface functionalization and charge. Besides Au-NPs, also other metal-based ENMs were integrated in this study. These include one type of titanium dioxide nanoparticle (TiO2-NP), zinc oxide nanoparticle (Zn-NP), as well as six silica nanoparticles (SiO2-NPs) with varying size and porosity. [...]