H2O2-Loaded Acoustic Phase-Change Nanoparticles Ehancing Coronary Micro-Circulation Thrombolysis: An in Vitro Study by Low Intensity Focused Ultrasound Irradiation

Abstract

Thrombolysis and oxygen (O2) supply in coronary micro-circulation are crucial for the treatment of acute myocardial infarction (AMI). The biochemical reaction synergized as cavitation effect of perfluoropentane (PFP) nanoparticles has the potential of targeted thrombolysis by ultrasound irradiation while H2O2 in the hydrogen peroxide solution provides O2 in coronary micro-embolization. Therefore, we sought to explore the clinical implication of hydrogen peroxide solution with PFP loaded nanoparticles to develop a novel plan for the treatment of coronary micro- embolization. Artery thrombosis was collected by carotid artery injury and stasis in 10 rabbits. H2O2/PFP nanoparticles (group A) were experimented in an in-vitro vascular system with Low Intensity Focused Ultrasound (LIFU) irradiation, comparing with PFP nanoparticles only (group B) and PBS buffer solution as control (group C). Group A, B and C circulated into the system where the thrombosis was placed in the middle. Thrombolysis ratios and pathological slides were analyzed. Dissolved Oxygen Detector (DOD) inspected the volume of O2 in the vascular system after LIFU exposure. The mean diameter and charge of the nanoparticles were (432.7± 26.8) nm and (-43.87±3.12) mV respectively, which showed uniform size and regular shape under the microscope. When the nanoparticles sonicated by LIFU, they changed phase gradually and transformed into microbubbles (MB). The results showed the highest efficiency of thrombolysis when the irradiation power and time were 5 w, 15 min. The dissolution ratios in group A (42.18±7.4) % was significantly larger than those in group B (29.26±3.2) % and C (7.24±2.63) % (p＜0.05). The pathological changes showed that in group A, a significant decrease of red blood cell in the thrombus was observed, and the structure of platelet were disorganized. Compared with group A, there was still considerable amount of red blood cells inside the thrombus with compact structure of platelet trabeculae in group B and C. The DOD showed that along with the increase of H2O2 concentration, the amount of O2 release was rising. For the sake of biosecurity and efficiency, 5% H2O2 was engaged in the experiment which can release (12.2±0.79) mg/L O2. H2O2/PFP nanoparticles with LIFU performed thrombolysis and provided O2 in coronary micro-circulation, which may establish a novel non-invasive primary treatment protocol of AMI.