In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles.
In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles.
复制标题
使用 Profilin-1 靶向磁性纳米颗粒对小鼠动脉粥样硬化特征进行体内 MR 和荧光双模态成像
作者：
Wang Y;Chen J;Yang B;Qiao H;Gao L;Su T;Ma S;Zhang X;Li X;Liu G;Cao J;Chen X;Chen Y;Cao F
目的：本研究旨在利用profin -1靶向磁性氧化铁纳米颗粒（PF1-Cy5.5-DMSA-Fe3O4-NPs，简称PC-NPs）作为多模态分子成像探针，通过磁共振成像（MRI）和近红外荧光（NIRF）探索动脉粥样硬化斑块的无创成像。方法与结果：通过缩合反应将多克隆profile -1抗体和nhss - cy5.5荧光染料偶联到dmsa - fe3o4纳米颗粒表面，构建PC-NPs。采用高脂高胆固醇饮食（HFD）诱导apoE-/-小鼠动脉粥样硬化模型16周。油红O染色检测主动脉斑块区域。分别采用免疫荧光染色和Western blot检测profin -1的表达。CCK-8法和跨井迁移法检测血管平滑肌细胞（VSMCs）的增殖情况。在静脉注射PC-NPs前和36 h后进行动脉粥样硬化斑块的体内MRI和NIRF成像。油红O染色显示HFD组斑块面积显著增加（p<0.05）。免疫荧光染色显示，HFD组斑块内大量存在profilin-1蛋白，并与α-平滑肌肌动蛋白共定位。Profilin-1 siRNA干预可抑制ox-LDL诱导的VSMCs增殖和迁移（p<0.05）。体内MRI和NIRF成像显示，PC-NPs在颈动脉粥样硬化斑块内积聚。注射PC-NPs动物的MRI信号与离体nif成像的荧光强度具有良好的相关性。结论：PC-NPs是一种很有前途的双模成像探针，可以提高斑块特征的分子诊断和动脉粥样硬化药物干预的评价。
Aims: This study aims to explore non-invasive imaging of atherosclerotic plaque through magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) by using profilin-1 targeted magnetic iron oxide nanoparticles (PF1-Cy5.5-DMSA-Fe3O4-NPs, denoted as PC-NPs) as multimodality molecular imaging probe in murine model of atherosclerosis. Methods and Results: PC-NPs were constructed by conjugating polyclonal profilin-1 antibody and NHS-Cy5.5 fluorescent dye to the surface of DMSA-Fe3O4-nanoparticles via condensation reaction. Murine atherosclerosis model was induced in apoE-/- mice by high fat and cholesterol diet (HFD) for 16 weeks. The plaque areas in aortic artery were detected with Oil Red O staining. Immunofluorescent staining and Western blot analysis were applied respectively to investigate profilin-1 expression. CCK-8 assay and transwell migration experiment were performed to detect vascular smooth muscle cells (VSMCs) proliferation. In vivo MRI and NIRF imaging of atherosclerotic plaque were carried out before and 36 h after intravenous injection of PC-NPs. Oil Red O staining showed that the plaque area was significantly increased in HFD group (p<0.05). Immunofluorescence staining revealed that profilin-1 protein was highly abundant within plaque in HFD group and co-localized with α-smooth muscle actin. Profilin-1 siRNA intervention could inhibit VSMCs proliferation and migration elicited by ox-LDL (p<0.05). In vivo MRI and NIRF imaging revealed that PC-NPs accumulated in atherosclerotic plaque of carotid artery. There was a good correlation between the signals of MRI and ex vivo fluorescence intensities of NIRF imaging in animals with PC-NPs injection. Conclusion: PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis.