Biomedical application of TiO2NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets.

Abstract

Background: Titanium dioxide nanoparticles (TiO₂NPs) 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 TiO₂NPs 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 TiO₂NP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiO₂NP 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 TiO₂NP treatment, which were crucial in TiO₂NP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiO₂NP 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 TiO₂NPs, specifically TiO₂NP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.