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Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Kristin Mohr, Maria Sommer, Grit Baier, Susanne Schöttler, Patricia Okwieka, Stefan Tenzer, Katharina Landfester, Volker Mailänder, Manfred Schmidt and Ralf Georg Meyer

The interactions between nanoparticles (NPs) and proteins in complex biological application media such as blood serum are capable of inducing aggregate formation which can lead to subsequent changes in biological activity. Here, we correlate surface charge, aggregation-tendency, and surface serum protein adsorption with cellular uptake and biodistribution in mice.
Polystyrene-based NPs (80 - 170 nm) with different surface functionalizations were synthesized and incubated with human serum. Interaction of NPs with serum proteins and aggregate formation were analyzed by mass spectrometryanalysis and dynamic light-scattering. Influence of surface functionalization on specific cellular uptake and organdistribution was characterized.
Localization and organ targeting of intravenously applied NPs preferentially depended on their aggregationbehavior in the presence of serum. Whereas strongly aggregating particles mainly located to liver, non-aggregating particles distributed to all organs. Determination of aggregate formation of NPs in the presence of serum and further analysis of the protein corona allows for pre-selection of NPs for in vivo application.