In vivo real-time red blood cell migration and microcirculation flow synergy imaging-surveyed thrombolytic therapy with iron-oxide complexes

Nanotherapeutics as a nascent method has attracted widely interest on the treatment of thrombosis. However, due to the limited temporal and spatial resolution of conventional imaging modalities, the dynamic visualization the thrombogenesis and evaluation of the effect of thrombolytic drugs are facing severely difficulties in vivo. In addition, the development of high targeting, short circulation time, and small size thrombolysis nanotherapeutics agents requires further research. Herein, we report a synergy imaging modality that combining a label-free capillary microscopy and laser speckle microcirculation imaging, which realized dynamic visualization of single red blood cell migration and large-field dynamic blood flow. In this work, we investigated the red blood cells migration and blood flow velocity response before and after treated through introducing a functional nano-thrombolytics, iron-oxide complexes coated urokinase (IPN@UK) on an orthotopic animal model in vivo. The functionalized IPN@UK nanocomposites exhibited outstanding thrombolysis effect. Significantly, whole-course changes, including red blood cell activity, complex thrombolytic therapeutics, were well surveilled and evaluated using dual-modality combining imaging strategy. These results show this synergy imaging strategy not only can achieve multiscale non-invasive visualization of dynamic thrombus events in real-time, but also can quantify hemodynamics information of thrombus. Our study demonstrates the potential of this synergy imaging method, which for early detection of thrombus, evaluation of the effect of drug thrombolysis, developing the thrombolytic drugs, and imaging-guide thrombolytic therapy in living systems.