Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, PR China; Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, PR China.
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Acta Biomater. 2019 May;90:324-336. doi: 10.1016/j.actbio.2019.04.014. Epub 2019 Apr 4.
Rupture of atherosclerotic plaques causes acute cardiovascular and cerebrovascular pathology. Tissue factor (TF) is a key factor that affects the development of atherosclerotic plaques and the formation of thrombus and thus constitutes a potential target for the detection of atherosclerotic plaques. In this study, the conjugation of the fusion protein 'enhanced green fluorescent protein with the first epidermal growth factor domain' (EGFP-EGF1) and superparamagnetic iron oxide nanoparticles (EGFP-EGF1-SPIONs) was explored for molecular imaging of TF-positive atherosclerotic plaques. EGFP-EGF1-SPIONs showed improved accuracy, superior contrast effects, and better cytocompatibility compared with common contrast agents in the detection of atherosclerotic plaques of apolipoprotein E knockout (ApoE) mice using magnetic resonance imaging. In conclusion, EGFP-EGF1-SPION is a promising TF-targeting nanoprobe to precisely and specifically detect atherosclerotic plaques, which may improve molecular imaging diagnosis of cardiovascular and cerebrovascular events for the comprehensive evaluation of atherosclerosis. STATEMENT OF SIGNIFICANCE: Traditional methods can only display the status of atherosclerosis, but not forecast the progress of lesions efficiently. It remains challenging to evaluate the plaques specifically and sensitively. In this study, we constructed a tissue factor-targeted magnetic nanoprobe to specifically detect plaques by magnetic resonance imaging in vivo, which will improve the diagnostic technology for atherosclerotic plaques and offer molecular level guidance to treat atherosclerosis. Furthermore, this strategy has critical clinical significance on prevention, diagnosis and therapeutic evaluation of cardio-cerebral vascular events.
动脉粥样硬化斑块的破裂会导致急性心血管和脑血管疾病。组织因子（TF）是影响动脉粥样硬化斑块发展和血栓形成的关键因素，因此构成了动脉粥样硬化斑块检测的潜在靶点。在这项研究中，探索了融合蛋白 '增强型绿色荧光蛋白与第一个表皮生长因子域'（EGFP-EGF1）与超顺磁性氧化铁纳米颗粒（EGFP-EGF1-SPIONs）的缀合，用于 TF 阳性动脉粥样硬化斑块的分子成像。与普通造影剂相比，EGFP-EGF1-SPION 用于载脂蛋白 E 敲除（ApoE）小鼠的磁共振成像检测动脉粥样硬化斑块时，具有更高的准确性、更好的对比效果和更好的细胞相容性。总之，EGFP-EGF1-SPION 是一种有前途的 TF 靶向纳米探针，可精确且特异性地检测动脉粥样硬化斑块，这可能会改善心血管和脑血管事件的分子成像诊断，从而全面评估动脉粥样硬化。
传统方法只能显示动脉粥样硬化的状态，但不能有效地预测病变的进展。特异性和敏感地评估斑块仍然具有挑战性。在这项研究中，我们构建了一种组织因子靶向磁共振纳米探针，通过体内磁共振成像特异性地检测斑块，这将提高动脉粥样硬化斑块的诊断技术，并为治疗动脉粥样硬化提供分子水平的指导。此外，该策略对心脑血管事件的预防、诊断和治疗评估具有重要的临床意义。
