CD40-targeting magnetic nanoparticles for MRI/optical dual-modality molecular imaging of vulnerable atherosclerotic plaques

Qimin Wu; Wei Pan; Guifu Wu; Fensheng Wu; Yousheng Guo; Xinxia Zhang

doi:10.1016/j.atherosclerosis.2023.02.008

CD40-targeting magnetic nanoparticles for MRI/optical dual-modality molecular imaging of vulnerable atherosclerotic plaques

Atherosclerosis. 2023 Mar:369:17-26. doi: 10.1016/j.atherosclerosis.2023.02.008. Epub 2023 Feb 23.

Authors

Qimin Wu¹, Wei Pan¹, Guifu Wu², Fensheng Wu¹, Yousheng Guo¹, Xinxia Zhang³

Affiliations

¹ Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518033, Guangdong, China.
² 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.
³ 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. Electronic address: zhangxx58@mail.sysu.edu.cn.

PMID: 36863196
DOI: 10.1016/j.atherosclerosis.2023.02.008

Abstract

Background and aims: 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.

Methods: 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.

Results: 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.

Conclusions: CD40-Cy5.5-SPIONs could potentially serve as an effective MRI/optical probe for vulnerable atherosclerotic plaques during non-invasive detection.

Keywords: Atherosclerosis; CD40-targeting magnetic nanoparticles; Dual-modality molecular imaging; Fluorescence imaging; Magnetic resonance imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atherosclerosis* / metabolism
Contrast Media / chemistry
Contrast Media / pharmacology
Magnetic Resonance Imaging / methods
Magnetite Nanoparticles*
Mice
Molecular Imaging
Nanoparticles* / chemistry
Plaque, Atherosclerotic* / metabolism

Substances

CY5.5 cyanine dye
Magnetite Nanoparticles
Contrast Media