Ultrasmall Nanoparticles Bind to Fibrinogen and Impair Normal Clot Formation

Abstract

The formation of a proper fibrin clot is essential during blood coagulation, as abnormal clots can predispose individuals to bleeding or thrombosis. Despite these concerns, there is currently limited understanding of the potential adverse effects of engineered nanomaterials on fibrin clot formation. This is surprising, given that fibrinogen is highly concentrated in plasma and has a large surface area, making it prone to unintended interactions with nanomaterials. In this study, the impact of ultrasmall gold nanoparticles (usGNPs) on fibrin clot formation is investigated. UsGNPs have gained significant interest in biomedical applications due to their unique physicochemical properties and favorable behavior in complex biofluids. It is found that the usGNPs interacted with fibrinogen, delayed the onset of clot formation, and became physically trapped within the forming fibrin matrix. Confocal microscopy showed that the usGNPs disrupted the normal architecture of the fibrin clot, resulting in a less dense network structure. This disruption led to larger clot pore sizes and increased clot permeability to liquid. Considering the potential health risks associated with abnormal clot formation, a detailed examination of the clot formation process should be included in the standard safety assessment of usGNPs and other nanomedicines.