低强度聚焦超声联合载过氧化氢相变纳米粒靶向助溶模拟冠状动脉循环的人工血管血栓栓塞

Objective To prepare a novel H₂O₂-loaded and phase-change nanoparticles, combined with low intensity focused ultrasound (LIFU) to dissolve intravascular thrombosis for the evaluation of its value in the treatment of coronary artery thrombolysis in the patients with acute myocardial infarction (AMI). Methods H₂O₂-loaded and phase-change nanoparticles were prepared by membrane hydration method. 50 ml arterial blood was collected from rabbit carotid artery and made into 400 - 800 mg thrombus blocks. They were divided into four groups randomly: poly butylene succinate buffer (PBS) solution as blank control (group A), SonoVue microbubbles group (group B), PFP phase-change nanoparticles group (group C), H₂O₂-loaded and phase-change nanoparticles group (group D). Each group of thrombus samples were placed into the artificial blood vessels of the extracorporeal thrombolysis simulation cycle device and combined with LIFU irradiation. The weights and pathological presentations were compared before and after thrombolysis. The volume of O₂in the vascular system was inspected using Dissolved Oxygen Detector (DOD) after LIFU exposure. Results The average size of H₂O₂-loaded nano-droplets was (456. 7 ± 31. 2)nm. Fluorescence microscopy showed that the structure of nanoparticles was stable and uniform in size. The weight loss and rates of thrombus in the four groups after thrombolysis were:group A (52.2 ± 11.5)mg, (9.7±3.5)%;group B (110.0 ± 21.9)mg, (19.4 ± 2.4)% ;group C (239.6 ± 46.3)mg, (39. 7 ±6.3)% and group D (309.8 ± 44. 8)mg, (54.2 ± 6.6)%, respectively. The weight loss and rates of thrombus in group C and D were higher than those in group A and B (all P <0.01), but there was no significant difference between group C and D (P >0.05). The DOD showed that along with the increase of H₂O₂concentration, O₂release was rising. Conclusions H₂O₂/PFP nanoparticles with LIFU performs efficient thrombolysis and provides O₂to improve hypoxia, which provides a potential novel treatment method for AMI patients with coronary embolism.