Effects of acute systemic administration of TiO₂, ZnO, SiO₂, and Ag nanoparticles on hemodynamics, hemostasis and leukocyte recruitment

Abstract

It has been suggested that engineered nanomaterials (ENM), once arrived in the circulation, may affect the cardiovascular system. The aim of this in vivo study was to screen major cardiovascular effects of acute systemic administration of a panel of five nanomaterials, TiO₂ anatase (NM-101), TiO₂ rutile (NM-104), ZnO (NM-110), SiO₂ (NM-200) and Ag (NM-300). Mice were anesthetized and the ENM were injected at a dose of 1 mg/kg via a catheter placed in the left femoral artery. Hemodynamic parameters were determined by invasive measurement of blood pressure and non-invasive measurement of heart rate. Ten minutes after injection of the ENM, the formation of light/dye-induced thrombi was assessed in the cremasteric microcirculation by intravital microscopy. In addition, the numbers of rolling, firmly adherent and transmigrated leukocytes were recorded in postcapillary cremasteric venules over a time period of 120 min after injection of ENM by intravital microscopy. The systemic administration of a single dose of the ENM tested did not dramatically alter hemodynamic parameters or affect early steps of leukocyte recruitment. However, the presence of circulating TiO₂ anatase, but not of TiO₂ rutile, SiO₂, ZnO or Ag nanoparticles, significantly accelerated thrombus formation in the murine microcirculation. Moreover, TiO₂ anatase but not TiO₂ rutile nanoparticles increased murine platelet aggregation in vitro. Taken together, only one of the five systemically administered ENM, TiO₂ anatase, affected hemostasis, whereas none of the ENM tested in this screening study dramatically modulated hemodynamic parameters or early steps of leukocyte recruitment.

• In vivo microscopy
• inflammation
• nanomaterials
• platelets
• thrombosis

Acknowledgements

The authors appreciate the technical assistance of Claudia Fahney and Gerhard Adams.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was funded by the EU FP7 project MARINA – Managing Risks of Nanomaterials (Grant no. 263215).