Nanoparticle Protein Interactions
For the delivery of bioactive compounds such as therapeutic proteins/peptides siRNA or drugs to a specific cell or organ, it is not only of great importance to improve the stability of the therapeutic agent during passage through the blood stream, but also to extend the circulation time in the body. Consequently the interaction with blood components has to be controlled to limit aggregation processes. Furthermore uptake in blood cells like macrophages has to be minimized. Only then the drug can reach the target cells.
A major focus is currently put on the defined analysis of the interaction of nanoparticles/nanocapsules with high concentrated protein solutions like blood serum or cytosol as well as with isolated proteins. Control of protein adsorption onto nanomaterials is especially important in the biomedical area. Our goal is the defined analysis of protein-polymer interactions by applying a combination of different physicochemical techniques to include dynamic and static light scattering (DLS/SLS), isothermal titration calorimetry (ITC), high pressure liquid chromatography (HPLC), asymmetric field flow fractionation (AF-FFF), mass spectrometry (LC-MS) and circular dichroism (CD) spectroscopy. Combination of these analytical methods allows us to address multiple aspects of protein-polymer interactions. We are one of a few research groups worldwide that are capable of performing multi-angle DLS on concentrated human blood serum as a routine measurement to monitor aggregation events between nanoparticles and human blood serum. Mass spectrometry (with the group of K. Müllen and with S. Tenzer from the University Medical Center Mainz) was used for the identification of adsorbed proteins on nanocapsules and for the first time for the determination of the adsorption kinetics. Using ITC we are first able to monitor binding kinetics between nanocapsules with whole serum as well as with specific proteins.
Understanding the details of the formation and the composition of the protein corona and also the consequences that are incurred by the specific proteins needs to be investigated further. The defined analysis of nanoparticle interactions might allow pre-selection of nanoparticles for in vivo application.