Construction of CNA35 Collagen-Targeted Phase-Changeable Nanoagents for LIFU-Triggered Ultrasound Molecular Imaging of Myocardial Fibrosis in Rabbits

Construction of CNA35 Collagen-Targeted Phase-Changeable Nanoagents for LIFU-Triggered Ultrasound Molecular Imaging of Myocardial Fibrosis in Rabbits
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DOI:
10.1021/acsami.9b05999
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发表时间:
2019
影响因子:
9.5
通讯作者:
Zhiyu Ling
Zhiyu Ling
中科院分区:
材料科学2区
文献类型:
--
作者:
Qin Zhou;Yalin Zeng;Qingsong Xiong;Shigen Zhong;Pan Li;Haitao Ran;Yuehui Yin;Chris Reutelingsperger;Frits W. Prinze;Zhiyu Ling

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Myocardial fibrosis plays an important role in the development of heart failure and malignant arrhythmia, which potentially increases the incidence of sudden cardiac death. Therefore, early detection of myocardial fibrosis is of great significance for evaluating the prognosis of patients and formulating appropriate treatment strategies. Late gadolinium-enhanced magnetic resonance imaging is considered as the currently effective strategy for noninvasive detection of myocardial fibrosis, but it still suffers some critical issues. In this work, a multifunctional liquid-gas phase-changeable type I collagen-targeted fluorocarbon nanoparticles (CNA35-PFP NPs) have been elaborately designed and constructed for molecular imaging of fibrotic myocardium based on ultrasound imaging. These as-constructed CNA35-PFP NPs are intravenously infused into rabbit circulation with animal model of myocardial infarction. Especially, these targeted CNA35-PFP NPs with nanoscale size could efficiently pass through the endothelial cell gap and adhere to the surface of fibroblasts in the fibrotic myocardium. Importantly, followed by low intensity focused ultrasound (LIFU) irradiation on the myocardium, these intriguing CNA35-PFP NPs could transform from liquid into gaseous microbubbles, which further significantly enhanced the ultrasound contrast in the fibrotic area, facilitating the detection by diagnostic ultrasound imaging. Therefore, this work provides a desirable noninvasive, economical and real-time imaging technique for the assessment of cardiac fibrosis with diagnostic ultrasound based on the rational design of liquid-to-gas phase-changeable nanoplatforms.