title: Metallic oxide nanoparticles stimulate blood coagulation independent of their surface charge.
abstract: Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, -28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
authors.affiliation: NMI Technology Transfer GmbH, Markwiesenstrasse 55, 72770, Reutlingen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Steuer
authors.forename: Rumen
authors.initials: R
authors.lastname: Krastev
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lembert
mesh_terms: D001777:Blood Coagulation; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D015034:Zinc Oxide
keywords: blood coagulation; coagulation; metal oxides; nanomaterials; nanoparticles; thrombogenicity; toxicity