Biomedical application of TiONPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets.

BACKGROUND

Titanium dioxide nanoparticles (TiONPs) are widely used in medical application. However, the relevant health risk has not been completely assessed, the potential of inducing arterial thrombosis (AT) in particular.

METHODS

Alterations in platelet function and susceptibility to arterial thrombosis induced by TiONPs were examined using peripheral blood samples from healthy adult males and an in vivo mouse model, respectively.

RESULTS

Here, using human platelets (hPLTs) freshly isolated from health volunteers, we demonstrated TiONP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiONP treatment increased the levels of glycoprotein IIb/IIIa and P-selectin leading to aggregation and activation of hPLTs, which were exacerbated by providing physiology-mimicking conditions, including introduction of thrombin, collagen, and high shear stress. Interestingly, intracellular calcium levels in hPLTs were increased upon TiONP treatment, which were crucial in TiONP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiONP treatment a reduction in mouse platelet (mPLT) counts, disrupted blood flow, and exacerbated carotid arterial thrombosis with enhanced deposition of mPLT.

CONCLUSIONS

Together, our study provides evidence for an ignored health risk caused by TiONPs, specifically TiONP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.