title: Size-dependent effects of nanoparticles on enzymes in the blood coagulation cascade.
abstract: 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.
authors.affiliation: Biochemistry and Structural Biology, Chemical Centre, Lund University , Lund, Sweden.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanfins
authors.forename: Cecilia
authors.initials: C
authors.lastname: Augustsson
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
authors.forename: Tommy
authors.initials: T
authors.lastname: Cedervall
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001779:Blood Coagulation Factors; D011137:Polystyrenes