Biomedical application of TiO₂NPs can cause arterial thrombotic risks through triggering procoagulant activity,...

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.

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.

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.

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.