The role of nanoparticle size in hemocompatibility.

It is expected that nanoparticular matters will be increasingly used for industrial and medical applications. Since it is known that nanoparticles exhibit unique and potential hazardous properties due to their small size, toxicity studies, risk assessment and risk management are of great interest. We focussed on adverse effects on human blood. Processes which warrant special attention are clotting, reactions triggering inflammatory and immune responses and hemolysis. Starting with the determination of size and surface charge in different media we assessed the effect of size and surface charge on induction of coagulation, thrombocyte activation, complement activation, granulocyte activation and hemolysis. We used polystyrene particles as model because they are available in different sizes but constant surface charges. The presence of salts and of protein in the dispersion solution increased particle size and neutralized surface charge. Positively charged particles formed aggregates in buffered solution. Interference of the particles with assays based on fluorescence associated cell sorting was identified. Positive surface charge induced activation of complement. Small size caused thrombocyte and granulocyte activation, and hemolysis. A characterization of particle size and surface charge in the solutions used for the experiments appears important for interpretation of the results. The size dependency of adverse effects in human blood is not linear; negatively charged particles larger than 60 nm hydrodynamic diameter appear to be considerably less hematotoxic than smaller ones.