Abstract:Object To investigate the correlation between the targeted depth and thrombolytic effect of fibrin-targeted liquid-gas phase-transitional (PT) nanoparticles (NPs) in arterial thrombosis. Methods Fibrin targeted PLGA-PFH-CREKA NPs was developed by double emulsification method, and its physical and chemical properties were verified. The preparation of arterial thrombosis were acquired through the New Zealand white rabbit, then the thrombi were collected in the non-phase-transitional (NPT) NPs, PT and non-targeted PT NPs respectively, LIFU with sound power density of 1 W/cm2 was used to irradiate outside. The quality of thrombi were recorded before and after the experiment, and frozen sections of blood clot were used to measure penetration depth by confocal microscope, the correlation between thrombolytic rate and the penetration depth of NPs was analyzed by linear regression analysis. Then the abdominal aortic thrombosis model was established in SD rats, fibrin targeted PT, non-targeted PT NPs were used to injected through rat tail vein respectively to evaluate the targeting ability in vivo. Result The PT fibrin targeted NPs were successfully prepared with a particle of 297.8±11.82 nm and a surface Zeta potential of 1.44±0.22 mV. This NPs also have a uniform spherical structure with good dispersibility. The thrombolysis rate (F=108.508,P<0.001) and penetration (F=96.187, P<0.001) of thrombus in the targeted PT group was significantly different from that in the non-targeted PT and NPT group. Moreover, linear regression showed a positive correlation between thrombus penetration depth and thrombolytic rate in the targeted PT group (R2=0.818, P<0.05). In the SD rat model of abdominal aortic thrombosis, the targeted PT group showed better fibrin targeting than the non-targeted PT group. Conclusion In this study, the targeting fibrin PT NPs were successfully prepared, which have a good targeting effect to thrombus fibrin, good thrombolytic effect, and good penetration to thrombus. Meanwhile, the thrombolytic rate is positively correlated with the penetration depth of thrombus in PT group.