The protein corona formed around nanoparticles in protein-rich fluids plays an important role for nanoparticle biocompatibility, as found in several studies during the last decade. Biological fluids have complex compositions and the molecular components interact and function together in intricate networks. Therefore, the process to isolate blood or the preparation of blood derivatives may lead to differences in the composition of the identified protein corona around nanoparticles. Here, we show distinct differences in the protein corona formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the ratio between particle surface area to protein concentration influences the detected corona. We also show that the nanoparticle size per se influences the formed protein corona due to curvature effects. These results emphasize the need of investigating the formation and biological importance of the protein corona in the same environment as the nanoparticles are intended for or released into.

Nanoparticles (NPs) are increasingly used in diagnostic and drug delivery. After entering the bloodstream, a protein corona will form around NPs. The size and curvature of NPs is one of the major characteristics affecting the composition of bound protein in the corona. Key initiators of the intrinsic pathway of blood coagulation, the contact activation complex, (Kallikrein, Factor XII, and high molecular weight Kininogen) have previously been identified on NPs surfaces. We show that the functional impact of carboxyl-modified polystyrene NPs on these initiators of the intrinsic pathway is size dependent. NPs with high curvature affect the enzymatic activity differently from NPs with low curvature. The size dependency is evident in full blood plasma as well as in solutions of single coagulation factors. NPs induce significant alteration of the enzymatic activity in a size-dependent manner, and enzyme kinetics studies show a critical role for NPs surface area and curvature.

Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both in the treatment and prevention of hemorrhagic complications due to hemophilia with inhibitor. In such cases, antihemophilic factors cannot be used. The normal physiology of factor VII/ factor VIIa (FVII/FVIIa) in the hemostatic process requires the presence of tissue factor (TF) that links to FVII leading to a FVIIa-TF complex which activates both factor X and factor IX. The therapeutic use of rFVIIa requires high amount of FVIIa. Some studies demonstrate that FVIIa at high doses still requires tissue factor for function, whereas others suggest that FVIIa activates FX directly on the platelet surface, in a TF-independent manner. In the present article, we discuss the arguments supporting both TF-dependent and TF-independent modes of action. Finally, the coexistence of both TF-dependent and TF-independent mechanisms cannot be excluded.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.