Precision Navigation of Venous Thrombosis Guided by Viscosity-Activatable Near-Infrared Fluorescence.

Abstract

Thrombus are blood clots formed by abnormal hemostasis in blood vessels and are closely associated with various diseases such as pulmonary embolism, myocardial infarction and stroke. Early diagnosis and treatment of thrombus is the key to reducing the high risk of thrombotic disease. Given that early thrombus is small in early size, free instability, wide regional distribution and fast formation, it is urgent to develop all-inclusive detection methods that combine high signal-to-noise ratio, in situ dynamic and rapid in-depth tissue imaging. Near-infrared (NIR) fluorescence imaging, with its excellent high spatiotemporal resolution and tissue penetration depth, is a powerful technique for direct visualization of thrombotic events in situ. Considering the fibrin highly expressed in the thrombus is a typical thrombotic target. Moreover, the viscosity of the thrombus is markedly higher than its surroundings. Therefore, we developed a fibrin-targeting and viscosity-activating thrombus NIR fluorescent probe (TIR-V) for high-resolution and high-sensitivity in situ lighten-up thrombus. TIR-V has the advantages of good thrombus targeting, significant "off-on" fluorescence specific response to viscosity, bright NIR fluorescence and good biocompatibility. The thrombus is clearly delineated by a high signal-to-noise ratio NIR fluorescence imaging, enabling imaging detection and precise navigation of thrombotic regions. This work demonstrates the potential of TIR-V as a bifunctional probe for definitive diagnostic imaging and direct navigation of thrombotic lesions in clinical applications.