Figure 4.

Effect of targeted and untargeted nanobubbles coated with recombinant tissue plasminogen activator (rtPA) (0,1 mg/g body weight) and of soluble rtPA (1 mg/g body weight) on thrombus dissolution and vascular occlusion in the rat antiphospholipd syndrome model. Thrombosis was induced by administration of anti(32 glycoprotein 1 (anti-(32-GPI) antibodies and treatment with thrombolytic agents was started after thrombus formation as detailed in the Methods. (A) Changes of fluorescence intensity of thrombi shown in the Online Supplementary Videos S3 to S5 during the first 15 minutes after thrombolytic treatment. Note the rapid and persistent decrease of fluorescence intensity in rats receiving targeted nanobubbles (rtPA-tNB), whereas soluble rtPA produced only a transient thrombolysis and untargeted NB (rtPA-NB) were ineffective. (B) Effect of NB and soluble rtPA on vascular occlusion during a 90-minute follow-up, as assessed by blood flow measurement. Consistent with the data of (A), only rtPA-tNB caused a marked and significant reduction of occluded vessels at all time points. The results in (B) are presented as mean ± standard deviation (SD) of experiments conducted in 3 rats. *P<0.05, **P<0.005 using one-way ANOVA followed by Student-Newman-Keuls test.