Monitoring reactive oxygen species (ROS) on the nanoscale - Combination of DNA origami and ceria nanoparticles

点击翻译按钮获取中文摘要

Ceria (CeO2) nanoparticles have attracted special interest because of their catalytic and free radical scavenging attributes. The ability of cerium to switch between two oxidation states (Ce3+ and Ce4+ ions) facilitates redox reactions at the nanoparticle surface or scavenging of reactive oxygen species (ROS) and producing relatively harmless, less reactive products. Doping lanthanide ions into ceria, e.g. Eu3+ ions, enhances its catalytic properties due to the increment of oxygen vacancies, providing more active sites for an overall increased redox activity. The project is aimed at determining/characterizing the protective potential of lanthanide doped ceria nanoparticles against ROS. Hydroxyl radicals as model ROS and ssDNA attached onto DNA origami templates to form an anchor for the ceria nanoparticles, which are surface-functionalized with complementary ssDNA, are used in the investigations. Eu3+-doped ceria nanoparticles will be synthesized by a non-hydrolytic sol-gel method and particle surface properties, spectroscopic properties and morphology, among other structural characteristics, will be determined. To achieve biocompatibility (and to combat the formation of protein corona for future use in body), the nanoparticles will be functionalized by ssDNA. Hydroxyl radicals will be generated by a Fenton mechanism. Triangular DNA origami templates will be fabricated and structurally characterized by AFM. ssDNA functionalized lanthanide-doped ceria will be placed onto the DNA-origamis via ssDNA linkers. The length of ssDNA strands will be used to modify the distance of the ceria nanoparticles to the DNA origami and subsequently a nm-scale is defined on which the reactivity of the hydroxyl radicals can be monitored. The ROS scavenging property of ceria will be evaluated on the nanoscale to develop a distance activity relationship, thereby determining the extent in which ceria can protect the ssDNA from hydroxyl radical damage. This will be assessed based on the level of damage observed on the ssDNA strands placed at various distances from the ceria nanoparticles, if any. Fluorescence measurements will be performed before and after the production of the ROS material and will be used in the assessment of the activity. AFM images after production of the hydroxyl radicals will be taken to determine the possible 'damage' on the DNA linkers and the DNA origami.