Stable Low-Dose Oxygen Release Using HO/Perfluoropentane Phase-Change Nanoparticles with Low-Intensity Focused Ultrasound for Coronary Thrombolysis.

After the onset of myocardial infarction, extensive coronary thrombus and oxygen supply insufficiency lead to severe myocardial damage and heart failure. Recently, ultrasound-irradiated phase-change nanoparticles have been recognized for their cardiovascular thrombolysis potential. Therefore, we sought to establish a novel treatment method using hydrogen peroxide (HO)/perfluoropentane (PFP) phase-change nanoparticles with low-intensity focused ultrasound (LIFU) for the simulation of acute coronary thrombolysis and myocardial preservation. There were three groups in our study: Group A consisted of phosphate-buffered saline (PBS) as the blank control, group B consisted of SonoVue microbubbles and group C consisted of HO/PFP phase-change nanoparticles. The HO/PFP phase-change nanoparticles were prepared using a double-emulsification process. The in vitro experiments were conducted in an artificial circulatory system connected to an LIFU system and dissolved oxygen detector. Thrombolysis efficiency and oxygen release efficiency were compared among the groups. HO/PFP nanoparticles with 3% HO (average size: 456.7 ± 31.2 nm, charge: -37.5 ± 5.22 mV) was the optimal selection in group C because of the stable loading capacity and stable low-dose oxygen release efficiency in the in vitro experiments. Thrombolytic weight loss and loss rates in group C (322.0 ± 40.8 mg, 54.8 ± 5.7%) were significantly higher than those in group A (36.2 ± 18.1 mg, 5.5 ± 2.5%) and group B (91.0 ± 11.9 mg, 14.3 ± 2.4%) (p < 0.01). The innovative method using HO/PFP phase-change nanoparticles with LIFU exhibited high thrombolytic efficiency and stable low-flow oxygen supply in the artificial circulatory system, providing a solid experimental foundation for the establishment of a novel treatment method for acute myocardial infarction.