新型液气相变双靶向纳米超声造影剂分子显像肿瘤细胞实验研究

With the rapid development of ultrasound molecular imaging technology, it is expected to become an effective tool for the early diagnosis of the tumor cells. However, commonly used micron-size ultrasound molecular probes could not pass through the vascular endothelial cell gap to reach the tumor cells, which is only limited for intravascular imaging. Therefore, it is an important issue to be studied in depth for seeking a nanoscale ultrasound contrast agent which is stable and able to cross the vascular endothelial cell gap to reach the tumor cells accurately. Based on our preliminary studies, this project intends to prepare a stable and tumor cell targeting perfluorocarbon nanoparticles, the nanoparticles can pass through the vascular endothelial cell gap and selectively concentrate on the surface of tumor cells. The nanoparticles can be used for two modes (ultrasound and magnetic resonance) molecular imaging of tumor cells. By low-intensity focused ultrasound irradiation, the liquid-gas phase transition can be occurred in liquid fluorocarbon nanoparticles, the mechanism of their enhancing ultrasound molecular imaging will be explored. At the same time, the influence of instantaneous impact on tumor cells, as well as the rules and mechanisms of microbubbles produced during the phase transition will be studied. We aim to develop a novel and efficient modality for the tumor diagnosis by molecular imaging , and to provide a novel molecular probe for early diagnosis of tumors.

随着超声分子成像技术的迅速发展，其有望成为对肿瘤细胞早期诊断的有效工具。但是，目前常用的微米级超声分子探针粒径大，不能穿过血管内皮细胞间隙到达肿瘤细胞，只能局限于血管内成像。因此，寻求一种稳定的、能穿过血管内皮细胞间隙准确到达肿瘤细胞的纳米级超声造影剂，是有待深入研究的重要课题。在前期研究的工作基础上，本课题拟制备一种稳定的、靶向肿瘤细胞的液态氟碳纳米粒，这种纳米粒能够穿越肿瘤血管内皮细胞间隙并选择性地浓聚于肿瘤细胞表面；该纳米粒以超声分子成像为核心，结合磁共振成像技术，对肿瘤细胞进行两种模式（超声、磁共振）分子成像；通过低强度聚焦超声的辐照，使液态氟碳纳米粒发生液气相变，研究其增强超声分子显像的机制；同时，研究相变过程中产生的瞬时冲击力对肿瘤细胞的影响，以及相变产生微泡的相关规律和机制；以期建立一种新型的、高效的肿瘤分子显像诊断模式，为肿瘤的早期诊断提供一种新的分子探针。

纳米级超声造影剂作为超声影像学最常用的探针，可以同时结合其他医学成像模式对同一研究对象进行成像，实现各种分子成像技术优势互补，成为医学影像学的研究热点之一。本项目制备一种能同时增强超声、磁共振、近红外荧光成像的多模态相变型造影剂，实现“一探针多模态”显像；在激光的触发下，造影剂发生液气相变，进一步增强超声显像效果；并且，其装载的磁共振及近红外荧光显像剂亦可作为光热治疗剂，在激光的激发下光热能量转化实现肿瘤光热消融治疗，从而成为集显像及治疗于一体的多功能造影剂，为肿瘤的早期诊断和治疗提供重要的实验依据。