H2 O2/PFP-loaded acoustic phase-change lipid nanoparticles enhancing thrombolysis in artificial vessel for simulation of coronary circulation:an in-vitro study by low intensity focused ultrasound irradiation / 中华超声影像学杂志

ABSTRACT

Objective To prepare a novel H2 O2-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 H2 O2-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 ) , H2 O2-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 O2 in the vascular system was inspected using Dissolved Oxygen Detector ( DOD) after LIFU exposure . Results The average size of H2 O2-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)％ ;groupB(110.0±21.9)mg,(19.4±2.4)％ ;groupC(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 H2O2 concentration ,O2 release was rising . Conclusions H2O2/PFP nanoparticles with LIFU performs efficient thrombolysis and provides O2 to improve hypoxia ,which provides a potential novel treatment method for AMI patients with coronary embolism .