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Nano Research 2020, 13(1): 173-182 https://doi.org/10.1007/s12274-019-2592-4
Research Article | Issue | Published: 19 December 2019

Molecular imaging of advanced atherosclerotic plaques with folate receptor-targeted 2D nanoprobes

Show Author's Information Zhide Guo1,§,  Liu Yang2,§,  Mei Chen3,4,§,  Xuejun Wen1,  Huanhuan Liu1,  Jingchao Li1,  Duo Xu1,  Yuanyuan An2,  Changrong Shi1,  Jindian Li1,  Xinhui Su5,  Zijing Li1,  Ting Liu1,  Rongqiang Zhuang1,  Nanfeng Zheng4( ),  Haibo Zhu2( ),  Xianzhong Zhang1( )
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
College of Materials Science and Engineering, Hunan University, Changsha 410082, China
The State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemistry, Xiamen University, Xiamen 361005, China
Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, China

§ Zhide Guo, Liu Yang, and Mei Chen contributed equally to this work.

Keywords:
two-dimensional (2D) material, atherosclerosis, folate receptor, multifunctional imaging, activated macrophages
Topics:
DiseasesMacrophagesMolecular imaging
Cite this article:
Guo Z, Yang L, Chen M, et al. Molecular imaging of advanced atherosclerotic plaques with folate receptor-targeted 2D nanoprobes. Nano Research, 2020, 13(1): 173-182. https://doi.org/10.1007/s12274-019-2592-4
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Abstract Full text Electronic supplementary material About this article

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 folic acid (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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Abstract
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Electronic supplementary material
About this article

Molecular imaging of advanced atherosclerotic plaques with folate receptor-targeted 2D nanoprobes

Show Author's information Zhide Guo1,§, Liu Yang2,§, Mei Chen3,4,§, Xuejun Wen1, Huanhuan Liu1, Jingchao Li1, Duo Xu1, Yuanyuan An2, Changrong Shi1, Jindian Li1, Xinhui Su5, Zijing Li1, Ting Liu1, Rongqiang Zhuang1, Nanfeng Zheng4( ), Haibo Zhu2( ), Xianzhong Zhang1( )
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
College of Materials Science and Engineering, Hunan University, Changsha 410082, China
The State Key Laboratory for Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemistry, Xiamen University, Xiamen 361005, China
Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, China

§ Zhide Guo, Liu Yang, and Mei Chen contributed equally to this work.

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 folic acid (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.

Keywords: two-dimensional (2D) material, atherosclerosis, folate receptor, multifunctional imaging, activated macrophages

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Publication history
Copyright
Acknowledgements

Publication history

Received: 21 October 2019
Revised: 28 November 2019
Accepted: 29 November 2019
Published: 19 December 2019
Issue date: January 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

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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