Wu Qimin, Pan Wei, Wu Guifu, Wu Fensheng, Guo Yousheng, Zhang Xinxia
Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518033, Guangdong, China.
Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518033, Guangdong, China; Guangdong Innovative Engineering and Technology Research Center for Assisted Circulation, Shenzhen, China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.
Atherosclerosis. 2023 Mar;369:17-26. doi: 10.1016/j.atherosclerosis.2023.02.008. Epub 2023 Feb 23.
Acute coronary syndrome caused by vulnerable plaque rupture or erosion is a leading cause of death worldwide. CD40 has been reported to be highly expressed in atherosclerotic plaques and closely related to plaque stability. Therefore, CD40 is expected to be a potential target for the molecular imaging of vulnerable plaques in atherosclerosis. We aimed to design a CD40-targeted magnetic resonance imaging (MRI)/optical multimodal molecular imaging probe and explore its ability to detect and target vulnerable atherosclerotic plaques.
CD40-Cy5.5 superparamagnetic iron oxide nanoparticles (CD40-Cy5.5-SPIONs), which comprise a CD40-targeting multimodal imaging contrast agent, were constructed by conjugating CD40 antibody and Cy5.5-N-hydroxysuccinimide ester with SPIONs. During this in vitro study, we observed the binding ability of CD40-Cy5.5-SPIONs with RAW 264.7 cells and mouse aortic vascular smooth muscle cells (MOVAS) after different treatments, using confocal fluorescence microscopy and Prussian blue staining. An in vivo study involving ApoE mice fed a high-fat diet for 24-28 weeks was performed. 24 h after intravenous injection of CD40-Cy5.5-SPIONs, fluorescence imaging and MRI were performed.
CD40-Cy5.5-SPIONs bind specifically to tumor necrosis factor (TNF)-α-treated macrophages and smooth muscle cells. Fluorescence imaging results showed that, compared with the control group and the atherosclerosis group injected with non-specific bovine serum albumin (BSA)-Cy5.5-SPIONs, the atherosclerotic group injected with CD40-Cy5.5-SPIONs had a stronger fluorescence signal. T2-weighted images showed that the carotid arteries of atherosclerotic mice injected with CD40-Cy5.5-SPIONs had a significant substantial T2 contrast enhancement effect.
CD40-Cy5.5-SPIONs could potentially serve as an effective MRI/optical probe for vulnerable atherosclerotic plaques during non-invasive detection.
由易损斑块破裂或糜烂引起的急性冠状动脉综合征是全球主要的死亡原因。据报道，CD40在动脉粥样硬化斑块中高表达，且与斑块稳定性密切相关。因此，CD40有望成为动脉粥样硬化中易损斑块分子成像的潜在靶点。我们旨在设计一种靶向CD40的磁共振成像（MRI）/光学多模态分子成像探针，并探索其检测和靶向易损动脉粥样硬化斑块的能力。
通过将CD40抗体和Cy5.5-N-羟基琥珀酰亚胺酯与超顺磁性氧化铁纳米颗粒（SPIONs）偶联，构建了包含靶向CD40的多模态成像造影剂的CD40-Cy5.5超顺磁性氧化铁纳米颗粒（CD40-Cy5.5-SPIONs）。在这项体外研究中，我们使用共聚焦荧光显微镜和普鲁士蓝染色观察了不同处理后CD40-Cy5.5-SPIONs与RAW 264.7细胞和小鼠主动脉血管平滑肌细胞（MOVAS）的结合能力。进行了一项体内研究，涉及给ApoE小鼠喂食高脂饮食24至28周。静脉注射CD40-Cy5.5-SPIONs 24小时后，进行荧光成像和MRI。
CD40-Cy5.5-SPIONs特异性结合肿瘤坏死因子（TNF）-α处理的巨噬细胞和平滑肌细胞。荧光成像结果显示，与注射非特异性牛血清白蛋白（BSA）-Cy5.5-SPIONs的对照组和动脉粥样硬化组相比，注射CD40-Cy5.5-SPIONs的动脉粥样硬化组具有更强的荧光信号。T2加权图像显示，注射CD40-Cy5.5-SPIONs的动脉粥样硬化小鼠的颈动脉有显著的T2对比增强效应。
CD40-Cy5.5-SPIONs在无创检测期间可能作为一种有效的MRI/光学探针用于易损动脉粥样硬化斑块。
