Tailored surface functionalization of inorganic nanoparticles for controlled protein adsorption and cellular uptake

• Applicant: Dr.-Ing. Fabian Meder
• Subject Area: Biomaterials
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250155084

The introduction of engineered nanoparticles into a biological environment leads to an uncontrolled adsorption of biomolecules like proteins onto the nanoparticle surface. Controlling this process is of utmost importance but as yet it has not been achieved: the adsorbed proteins impact all subsequent reactions of the nanoparticles in the biological environment, for example their uptake by cells. It determines thereby also the nanoparticles' toxicity and biocompatibility, and the prospects of success of many biotechnological and biomedical applications of nanoparticles. Which proteins adsorb onto the nanoparticles depends strongly on the nanoparticle surface chemistry, which can be altered by chemical functionalization. As shown in preliminary experiments, tailoring the concentration of negatively charged sulfonate groups on the surface of nanoparticles allows to increase the adsorption amount of proteins with a high proportion of positively charged amino acids. Regrettably, it is widely unknown, how the concentration and distribution of such nanoparticle surface groups are 'recognized' by particular proteins in complex protein mixtures (like blood), and why even small variations of such functional groups shape the protein adsorption layer and affect nanoparticle-cell interactions. This will be investigated further in the proposed project. For this, alumina, silica, and gold nanoparticles will be surface-functionalized with different concentrations of suffocate surface groups between no sulfonate groups and a monolayer. Particles with sulfonate group concentrations in between these two extremes have a tailored multifunctional surface chemistry consisting of sulfonate groups and remaining unfunctionalized particle core material. Then the nanoparticle-protein interactions in human serum will be determined to analyse which proteins recognize the different proportions of particle surface groups, vary their adsorption, and which protein properties lead to this behaviour. In addition, in order to analyse the impact of the surface functionalization on nanoparticle-cell interactions it will be determined how the functionalized nanoparticles are taken up by endothelial cells. The proposed project enables to develop fundamental surface design strategies of nanoparticles for targeted interactions with proteins and cells.

• DFG Programme: Research Fellowships
• International Connection: Ireland
• Host: Professor Dr. Kenneth A. Dawson