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

Zhide Guo; Liu Yang; Mei Chen; Xuejun Wen; Huanhuan Liu; Jingchao Li; Duo Xu; Yuanyuan An; Changrong Shi; Jindian Li; Xinhui Su; Zijing Li; Ting Liu; Rongqiang Zhuang; Nanfeng Zheng; Haibo Zhu; Xianzhong Zhang

doi:10.1007/s12274-019-2592-4

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Research Article

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

Zhide Guo^{¹^,^§}, Liu Yang^{²^,^§}, Mei Chen^{³^,⁴^,^§}, Xuejun Wen^¹, Huanhuan Liu^¹, Jingchao Li^¹, Duo Xu^¹, Yuanyuan An^², Changrong Shi^¹, Jindian Li^¹, Xinhui Su^⁵, Zijing Li^¹, Ting Liu^¹, Rongqiang Zhuang^¹, Nanfeng Zheng^⁴(

), Haibo Zhu^²(

), Xianzhong Zhang^¹(

)

1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

2State 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

3College of Materials Science and Engineering, Hunan University, Changsha 410082, China

4The 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

5Zhongshan Hospital Affiliated to Xiamen University, Xiamen 361004, China

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

Show Author Information

Graphical Abstract

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 folate receptor multifunctional imaging activated macrophages atherosclerosis

Electronic Supplementary Material

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Nano Research

Volume 13 Issue 1,
January 2020

Pages 173-182

DOI: 10.1007/s12274-019-2592-4

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

Topics:

Diseases Macrophages Molecular imaging

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Received: 21 October 2019

Revised: 28 November 2019

Accepted: 29 November 2019

Published: 19 December 2019