Nanoscaled ultrasound contrast agents for enhanced sonothrombolysis

Sonothrombolysis, the enhancement of thrombolysis with ultrasound (US), is widely used in clinical practice. The use of an ultrasound contrast agent can lead to a further reduced recanalization time of the occluded blood vessel and thus to better outcome for the patient. In this study the sonothrombolytic efficacy of our new nanoscaled ultrasound contrast agent (NUSCA) was investigated. This new contrast agent has a size of less than 100 nm and should thus be able to penetrate the thrombus and achieve a thrombolysis from inside out. In this study human whole blood clots were exposed to US, US and NUSCA, US and recombinant tissue plasminogen activator (rt-Pa) or urokinase (UK), or a combination of US, NUSCA and thrombolytic drug in a closed-loop flow model. We sonicated with diagnostic US at a frequency of 2.85 MHz for 30 min. Clot mass loss of 50.6 ± 6.0% for the combination of US, NUSCA and rt-PA was found. Using UK as thrombolytic drug 57.7 ± 9.0% clot mass loss could be seen. Thus the weight loss exceeded the conventional values of up to 30%. Scanning electron microscopy (SEM) images revealed changes of the fibrin network on the thrombus surface. The NUSCA was able to loosen the network and induce large pores in the thrombus surface. The high rates of clot mass loss and the obvious changings of fibrin structure make our NUSCA a promising tool for sonothrombolytic therapy.