多模态双靶点液态氟碳分子探针用于血栓显像与治疗的基础研究

动脉血栓形成严重危害人类健康，研发高效、灵敏、特异性高的分子探针，能够实现在体无创性早期诊断、及时治疗以挽救缺血坏死的组织，减少并发症，降低死亡率。本项目结合MR、超声及光声学成像技术优势及前期研究基础，拟构建集诊疗为一体的多模态双靶点分子探针。壳材料PLGA携带Fe3O4，可以同时行MR和光声学成像，核心包载相变材料全氟己烷（PFH），通过低强度聚焦超声（LIFU）致相变技术（ADV），在超声显像血栓的同时，对血栓组织结构行损毁术定向破坏血栓，使其成为多功能分子探针。该探针表面同时共价结合靶向P-选择素的EWVDV和靶向整合素αIIbβ3的cRGD肽段，能够模拟白细胞附壁过程，抵抗动脉血流高剪切力的冲刷，增强其靶向性。通过体内外实验验证其靶向性及多模态分子显像效果，研究相变溶栓效果及其溶栓机制，为分子水平诊断血栓，为溶栓治疗及其活体动态监测提供一种简便、有效、安全、无创的新方法。

Arterial thrombosis is extremely harmful to human health, development of an efficient, sensitive and highly specific molecular probe can achieve the noninvasive, early diagnosis and timely treatment in vivo and revive the ischemic tissues and reduce complications and mortality. This study combines the advantages of MRI, ultrasound and photoacoustic imaging and our pilot research to construct a multi-modal dual target molecule probe for the diagnosis and treatment of thrombosis. Shell material carrying Fe3O4 can be used both for MRI and photoacoustic imaging. Through the acoustic droplet vaporization (ADV) with low-intensity focused ultrasound (LIFU), the phase-transition material, perfluorohexane (PFH) decorated in the core makes the probe capable of showing the thrombus under ultrasound and destructing the thrombus in the same time. These functions make it a multi-functional probe. The surface of the probe is modified simultaneously by EWVDV peptide targeted to P-selectin and cRGD peptide targeted to integrin αIIbβ3. It can emulate the efficacy of leukocyte homing mechanisms, offset the artery high shear flow and enhance its targeting. The targeting to thrombosis and the multi-modal molecular imaging will be confirmed in vitro and in vivo experiments, the thrombolytic therapy mechanism will be studied further. This study will provide a new molecular diagnostic technology, a simple, effective, safe and non-invasive method for thrombolytic therapy and in vivo dynamic monitoring. This promotes the development of thrombolytic therapy.