Vulnerable atherosclerotic plaques are responsible for most cardiovascular diseases (CVDs). Folate receptor (FR) positive activated macrophages were thought to be a prominent component in the development of vulnerable plaque. The objective of this study is to develop folate conjugated two-dimensional (2D) Pd@Au nanomaterials (Pd@Au-PEG-FA) for targeted multimodal imaging of the FRs in advanced atherosclerotic plaques. Pharmacokinetic and imaging studies (single photon emission computed tomography (SPECT), computed tomography (CT) and photoacoustic (PA) imaging) were performed to confirm the prolonged blood half-life and enrichment of radioactivity in atherosclerotic plaques. Strong signals were detected in vivo with SPECT, CT and PA imaging in heavy atherosclerotic plaques, which were significantly higher than those of the normal aortas after injection of Pd@Au-PEG-FA. Blocking studies with preinjection of excess FA could effectively reduce the targeting ability of Pd@Au-PEG-FA in atherosclerotic plaques, further demonstrating the specific binding of Pd@Au-PEG-FA for plaque lesions. Histopathological characterization revealed that the signal of probe was in accordance with the high-risk plaques. In summary, the Pd@Au-PEG-FA has favorable pharmacokinetic properties and provides a valuable approach for detecting high-risk plaques in the presence of FRs in atherosclerotic plaques.

中文翻译：

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叶酸受体靶向的二维纳米探针对晚期动脉粥样硬化斑块的分子成像

易碎的动脉粥样硬化斑块是导致大多数心血管疾病（CVD）的原因。叶酸受体（FR）阳性活化的巨噬细胞被认为是易损斑块形成的重要组成部分。这项研究的目的是开发叶酸共轭二维（2D）Pd @ Au纳米材料（Pd @ Au-PEG-FA），用于晚期动脉粥样硬化斑块中FR的靶向多峰成像。进行了药代动力学和成像研究（单光子发射计算机断层扫描（SPECT），计算机断层扫描（CT）和光声（PA）成像）以确认延长的血液半衰期和动脉粥样硬化斑块中放射性的富集。在体内检测到强信号SPECT，CT和PA显像在重度动脉粥样硬化斑块中，显着高于注射Pd @ Au-PEG-FA后的正常主动脉斑块。预注射过量FA的阻断研究可以有效降低Pd @ Au-PEG-FA在动脉粥样硬化斑块中的靶向能力，进一步证明Pd @ Au-PEG-FA对斑块病变的特异性结合。组织病理学特征表明探针信号与高危斑块一致。总之，Pd @ Au-PEG-FA具有良好的药代动力学特性，为在动脉粥样硬化斑块中存在FRs时检测高危斑块提供了有价值的方法。