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

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; p. 296
• Main Authors: Zhang, Liwei, Xue, Sheng, Ren, Feng, Huang, Siyang, Zhou, Ruizhi, Wang, Yu, Zhou, Changyong, Li, Zhen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28.09.2021; BioMed Central; BMC
• Subjects: Adaptive immunity; Animals; Antibodies; Antigenic determinants; Apolipoprotein E; Apolipoproteins E - metabolism; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - diagnostic imaging; Atherosclerosis - therapy; Atherosclerotic plaque; Binding sites; Cardiovascular disease; Care and treatment; Cholesterol; Coronary vessels; Diagnosis; Disease Models, Animal; Epitopes; Epitopes - metabolism; Ethanol; Fatty acids; Health aspects; Humans; Identification and classification; imaging; Immune response; Infrared windows; Libraries; Lipoproteins; Lipoproteins, LDL; Low density lipoprotein; Macrophages; Macrophages - metabolism; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy; Male; Medical research; Medicine, Experimental; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Molecular probes; Nanoparticles; Near infrared radiation; Oxidation; Oxidation-reduction reaction; oxidation-specific epitopes; Phages; Physiological aspects; Plaque, Atherosclerotic - diagnostic imaging; Plaque, Atherosclerotic - therapy; Plaques; Polymers; Single-Chain Antibodies; single-chain variable fragment antibody; therapy; Transcriptomes; Vein & artery diseases; Viral antibodies; China; Beijing China; United States > US; atherosclerosis; single-chain variable fragment antibody; imaging; therapy; oxidation-specific epitopes
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-01047-4

Oxidation-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. Here, 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 NaNdF @NaGdF nanoparticles for noninvasive imaging of atherosclerotic plaques by magnetic resonance (MR) and near-infrared window II (NIR-II) imaging. Together, these data demonstrate the potential of ASA6 antibody in targeted therapy and noninvasive imaging for atherosclerosis.