Stable Low-Dose Oxygen Release Using H2O2/Perfluoropentane Phase-Change Nanoparticles with Low-Intensity Focused Ultrasound for Coronary Thrombolysis

Nan Jiang; Bo Hu; Sheng Cao; Shunji Gao; Qingqiong Cao; Jinling Chen; Qing Zhou; Ruiqiang Guo

doi:10.1016/j.ultrasmedbio.2020.06.004

Stable Low-Dose Oxygen Release Using H₂O₂/Perfluoropentane Phase-Change Nanoparticles with Low-Intensity Focused Ultrasound for Coronary Thrombolysis

Ultrasound Med Biol. 2020 Oct;46(10):2765-2774. doi: 10.1016/j.ultrasmedbio.2020.06.004. Epub 2020 Jul 7.

Authors

Nan Jiang¹, Bo Hu², Sheng Cao¹, Shunji Gao³, Qingqiong Cao¹, Jinling Chen¹, Qing Zhou¹, Ruiqiang Guo¹

Affiliations

¹ Echo Lab, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China.
² Echo Lab, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: krishu@whu.edu.cn.
³ Department of Ultrasound Imaging, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

PMID: 32646686
DOI: 10.1016/j.ultrasmedbio.2020.06.004

Abstract

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 (H₂O₂)/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 H₂O₂/PFP phase-change nanoparticles. The H₂O₂/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. H₂O₂/PFP nanoparticles with 3% H₂O₂ (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 H₂O₂/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.

Keywords: Coronary thrombolysis; Microcirculation; Nanoparticle; Oxygen release; Ultrasound irradiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Coronary Thrombosis / therapy*
Fluorocarbons*
Hydrogen Peroxide*
Mechanical Thrombolysis / methods*
Microbubbles*
Nanoparticles*
Oxygen / administration & dosage*
Phase Transition
Rabbits
Ultrasonic Waves*

Substances

Fluorocarbons
perfluoropentane
Hydrogen Peroxide
Oxygen