In vitro and in vivo fate of composite nanoparticles observed in situ with triple labelling techniques

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The fate of inorganic nanoparticles after their uptake by cells/organisms will be investigated. Two material systems will be developed. Individual nanoparticles will comprise an inorganic core, an organic surface coating, as a corona of adsorbed proteins. Triple labelling of all parts, i.e. core, surface coating, and protein corona, will be developed. Composite nanoparticles will comprise multiple individual inorganic nanoparticles embedded/integrated in a polymer matrix, surrounded by a corona of adsorbed proteins. Triple labelling of all parts, i.e. core and surface of the inorganic nanoparticles, and the polymer matrix, will be developed. Labels for different detection modalities comprising fluorescence, SERS, MRI, SPECT, and PET will be used. Cells and organisms (hydra, chicken embryos) will be exposed to the nanoparticles. The fate and biodistribution of all individual compounds of the nanoparticles will be traced, allowing for observing possible degradation of the nanoparticles inside cells/organisms. In this way physicochemical properties, as in particular integrity of the nanoparticles will be determined not before, but after internalization of the particles. The results will help to better understand the concept of passive versus active targeting, e.g. address the question whether degradation of the organic surface coating around nanoparticles interferes with active targeting. In addition the strategy to deliver composite nanoparticles which are big enough for passive targeting, but which after degradation to their components are small enough for complete excretion, will be investigated. Besides labels providing contrast for imaging also active labels will be used, which change their signal in dependence of their local environment. In this way a constant monitoring of the local environment around all the components of the nanoparticles will be achieved (such as probing for ROS).