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
复制标题
CNA35 胶原蛋白靶向相变纳米制剂的构建，用于兔心肌纤维化的 LIFU 超声分子成像
DOI：
10.1021/acsami.9b05999
复制
发表时间：
2019
影响因子：
9.5
通讯作者：
Zhiyu Ling
中科院分区：
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
心肌纤维化在心力衰竭和恶性心律失常的发生发展中起重要作用，可能增加心源性猝死的发生率。因此，早期发现心肌纤维化对评估患者预后和制定适当的治疗策略具有重要意义。晚期钆增强磁共振成像被认为是目前无创检测心肌纤维化的有效方法，但仍存在一些关键问题。在这项工作中，一个多功能的液-气相变I型胶原靶向碳氟纳米粒子（CNA 35-PFP NPs）已精心设计和构建的纤维化心肌的分子成像的基础上超声成像。将这些构建的CNA 35-PFP纳米粒静脉输注到具有心肌梗死动物模型的兔循环中。特别是，这些具有纳米尺寸的靶向CNA 35-PFP纳米颗粒可以有效地穿过内皮细胞间隙并粘附到纤维化心肌中的成纤维细胞表面。重要的是，在低强度聚焦超声（LIFU）照射心肌后，这些有趣的CNA 35-PFP纳米颗粒可以从液体转化为气态微泡，这进一步显著增强了纤维化区域的超声对比度，便于通过诊断超声成像进行检测。因此，这项工作提供了一个理想的非侵入性，经济和实时成像技术的基础上合理设计的液-气相变纳米平台的诊断超声心脏纤维化的评估。
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.