An atherosclerotic plaque-targeted single-chain antibody for MR/NIR-II imaging of atherosclerosis and anti-atherosclerosis therapy

Liwei Zhang,Zhen Li,Siyang Huang,Sheng Xue,Feng Ren,Changyong Zhou,Ruizhi Zhou,Yu Wang

doi:10.1186/s12951-021-01047-4

Abstract

BackgroundOxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques. Innate and adaptive immune responses to OSEs play an important role in atherosclerosis. The purpose of this study was to develop novel human single-chain variable fragment (scFv) antibody specific to OSEs to image and inhibit atherosclerosis.ResultsHere, we screened a novel scFv antibody, named as ASA6, from phage-displayed human scFv library. ASA6 can bind to oxidized LDL (Ox-LDL) and atherosclerotic plaques. Meanwhile, ASA6 can also inhibit the uptake of Ox-LDL into macrophage to reduce macrophage apoptosis. The atherosclerotic lesion area of ApoE−/− mice administrated with ASA6 antibody was significantly reduced. Transcriptome analysis reveals the anti-atherosclerosis effect of ASA6 is related to the regulation of fatty acid metabolism and inhibition of M1 macrophage polarization. Moreover, we conjugated ASA6 antibody to NaNdF4@NaGdF4 nanoparticles for noninvasive imaging of atherosclerotic plaques by magnetic resonance (MR) and near-infrared window II (NIR-II) imaging.ConclusionsTogether, these data demonstrate the potential of ASA6 antibody in targeted therapy and noninvasive imaging for atherosclerosis.Graphic abstract

Highlights

Oxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques
We found ASA6 antibody could bind to oxidized low density lipoprotein (LDL) (Ox-LDL) and inhibit the uptake of Ox-LDL by macrophages to reduce the apoptosis of macrophages
The biocompatibility of ASA6‐NPs probe Firstly, we evaluated the toxicity of ASA6-NPs probe to the human aortic endothelial cells (HAEC) in vitro, for the reason that the probe was directly injected into circulation system during targeted magnetic resonance (MR)/near-infrared window II (NIR-II) imaging

Summary

Introduction

Oxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques. Cardiovascular disease (CVD) is the leading cause of death worldwide which result in ≈ 17.8 million deaths globally, and the crude prevalence of CVD was 485.6 million cases in 2017 [1]. Atherosclerosis is a chronic inflammatory disease of arteries and is the most common underlying cause of CVDs [2]. The continuous engulfment of Ox-LDL mediated by scavenger receptors (e.g. CD36 and SRA1) leads to the transformation of macrophages into foam cells, which are the characteristic cells in the atherosclerotic lesions [8]. Ox-LDL could induce chronic inflammation and eventually result in the initiation and progression of atherosclerotic lesions [9, 10]

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