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

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.

心肌纤维化在心力衰竭和恶性心律失常的发展中起重要作用，这可能会增加心脏性猝死的发生率。因此，早期检测心肌纤维化对于评估患者预后和制定适当的治疗策略具有重要意义。延迟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，但它仍然存在一些关键问题。在这项工作中，精心设计并构建了一种多功能液 - 气相变的I型胶原靶向氟碳纳米颗粒（CNA35 - PFP纳米粒），用于基于超声成像的纤维化心肌分子成像。将这些构建好的CNA35 - PFP纳米粒静脉注入患有心肌梗死动物模型的兔体内循环。特别是，这些具有纳米级尺寸的靶向CNA35 - PFP纳米粒能够有效地穿过内皮细胞间隙并附着在纤维化心肌中的成纤维细胞表面。重要的是，在对心肌进行低强度聚焦超声（LIFU）照射后，这些有趣的CNA35 - PFP纳米粒能够从液体转变为气态微泡，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，这项工作基于合理设计的液 - 气相变纳米平台，为利用诊断超声评估心肌纤维化提供了一种理想的无创、经济且实时的成像技术。