Abstract
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.
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Acknowledgements
This study was financially supported by the National Postdoctoral Program for Innovative Talents (No. BX201700142), Postdoctoral Science Foundation of China (No. 2018M630732), the National Natural Science Foundation of China (Nos. 81901805, 21906135, 81471707, 21705037, and 91539126), Hunan Provincial Natural Science Foundation of China (No. 2018JJ3092), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2016-I2M-1-009), and Drug Innovation Major Project (2018ZX09711001-003-011).
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X. Z. Z., H. B. Z., and N. F. Z. were responsible for the conception and design of the study, the drafting of the manuscript, and final approval of the version to be published. Z. D. G., L. Y., and M. C. were responsible for the the acquisition, analysis and interpretation of the data, and the drafting of the manuscript. R. Q. Z., T. L., and Z. J. L. contributed to critical revision for important intellectual content, and final approval of the version to be published. X. H. S. contributed to critical revision of the manuscript for important intellectual content and material support. X. J. W., J. C. L., and D. X. assisted in the synthesis of probes. US and PA imaging was done by H. H. L., Y. Y. A., C. R. S., and J. D. L. directed the histopathological characterization of animal models.
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Guo, Z., Yang, L., Chen, M. et al. Molecular imaging of advanced atherosclerotic plaques with folate receptor-targeted 2D nanoprobes. Nano Res. 13, 173–182 (2020). https://doi.org/10.1007/s12274-019-2592-4
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DOI: https://doi.org/10.1007/s12274-019-2592-4