OCT/MRI联合成像评估靶向MMPs诊疗一体化纳米探针对易损斑块稳定性的影响

Coronary heart diseases are always the leading cause of death worldwide. Rupture of vulnerable plaque is a common pathological basis of cardiovascular disease and remains the leading cause of mortality. Therefore, how to achieve the goal of early diagnosis of vulnerable plaque is still an essential clinical issue. Optical coherence tomography (OCT) is an intravascular imaging technique with high resolution, which plays an important role in the diagnosis of different plaques in coronary artery disease. However, it is usually not possible to obtain information on the underlying molecular and cellular aspects of atherosclerosis (AS) plaques via OCT imaging. Magnetic resonance imaging (MRI) is technically advantageous in discriminating among tissues with high resolution, which can be used to characterize the morphology and composition of AS plaques. So, combined OCT and MR molecular imaging allows intravascular imaging of biological detail in vulnerable plaque. Matrix metalloproteinases (MMPs) are closely associated with the formation and stability of vulnerable plaques. In our current research, we focus on the effects of MMP-2 and MMP-9 in AS plaque, which are selected as molecular imaging and treating targets. To render ultrasmall superparamagnetic iron oxide (USPIO) particles specific for the extracellular MMPs, the MMPs-cleavable peptide modified with polyethylene glycol, yielding a MRI reporter (Fe3O4/PEI-MMPsC-PEG) for MR imaging, which can be used for assessing vulnerable plaque characteristics. In addition, miR-124 will be loaded into the prepared nanoscale probe and yield an integrated probe for AS diagnosis and treatment, which can directly repress MMPs expression in vulnerable plaque. Last, we will evaluate therapeutic effect of the integrated probe by OCT/MRI bimodal imaging and pathological analysis.

冠心病仍是威胁人类健康的首要原因。易损斑块破裂是引起冠心病患者的重要死因。如何尽早识别易损斑块是目前心血管领域亟待解决的科学问题。OCT可在体识别易损斑块微结构特征，却难以评估斑块内分子成分。MRI分子成像能从分子水平揭示易损斑块特点。因此，联合OCT/MRI成像可提供斑块解剖结构及分子成分信息，增强其检测能力。MMPs与斑块形成及稳定密切相关，项目组拟以MMPs作为斑块成像及治疗靶点。前期我们成功利用聚乙烯亚胺（PEI）修饰USPIO的纳米粒子，将其与PEG链接的MMPs可剪切肽桥连成MMPs可控的纳米颗粒，构建新型MRI分子成像探针Fe3O4/PEI-MMPsC-PEG。此外，miR-124作为MMPs靶向基因疗法，载入已制备的新型纳米探针，开发新型的靶向MMPs的诊疗一体化体系。项目拟联合OCT/MRI成像及病理分析，实现斑块结构及分子成分可视化，评估此新型探针对易损斑块的疗效。

冠心病仍是威胁人类健康的首要原因。易损斑块破裂是引起冠心病患者的重要死因。如何尽早识别易损斑块是目前心血管领域亟待解决的科学问题。OCT可在体识别易损斑块微结构特征，却难以评估斑块内分子成分。MRI分子成像能从分子水平揭示易损斑块特点。因此，联合OCT/MRI成像可提供斑块解剖结构及分子成分信息，增强其检测能力。MMPs与斑块形成及稳定密切相关，项目组拟以MMPs作为斑块成像及治疗靶点。前期我们成功利用聚乙烯亚胺（PEI）修饰USPIO的纳米粒子，将其与PEG链接的MMPs可剪切肽桥连成MMPs可控的纳米颗粒，构建新型MRI分子成像探针Fe3O4/PEI-MMPsC-PEG。此外，miR-124作为MMPs靶向基因疗法，载入已制备的新型纳米探针，开发新型的靶向MMPs的诊疗一体化体系。项目拟联合OCT/MRI成像及病理分析，实现斑块结构及分子成分可视化，评估此新型探针对易损斑块的疗效。