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Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors

Journal article
Authors M. Ahmed
R. Baumgartner
S. Aldi
P. Dusart
U. Hedin
B. Gustafsson
Kenneth Caidahl
Published in International Journal of Nanomedicine
Volume 14
Pages 3723-3741
ISSN 1176-9114
Publication year 2019
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 3723-3741
Language en
Links dx.doi.org/10.2147/IJN.S197990
Keywords Atherosclerosis, Inflammation, Macrophage, Molecular imaging, Scavenger receptor, Zirconium, CD36 antigen, fluorescent dye, human serum albumin, low density lipoprotein, oxidized low density lipoprotein receptor 1, scavenger receptor A, scavenger receptor A1, scavenger receptor B, scavenger receptor B2, unclassified drug, zirconium 89, aconitylation, Article, CD36 gene, cell interaction, cell transport, confocal microscopy, controlled study, endothelium cell, flow cytometry, fluorescence imaging, gene, gene knockdown, human, human cell, in vitro study, isotope labeling, maleylation, microscopy, MSR1 gene, ORL1 gene, protein modification, protein targeting, radiation measurement, RNA interference, smooth muscle cell, THP-1 cell line, vascular disease
Subject categories Internal medicine

Abstract

Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifications of human serum albumin (HSA) could be used to target macrophages efficiently in vitro. Materials and methods: Maleylated and aconitylated HSA were compared with unmodified HSA. Fluorescent or radiolabeled (89 Zr) modified HSA was used in in vitro experiments to study cellular uptake by differentiated THP-1 cells and primary human macrophages. The time course of uptake was evaluated by flow cytometry, confocal microscopy, real-time microscopy and radioactivity measurements. The involvement of scavenger receptors (SR-A1, SR-B2, LOX-1) was assessed by knockdown experiments using RNA interference, by blocking experiments and by assays of competition by modified low-density lipoprotein. Results: Modified HSA was readily taken up by different macrophages. Uptake was mediated nonexclusively via the scavenger receptor SR-A1 (encoded by the MSR1 gene). Knockdown of CD36 and ORL1 had no influence on the uptake. Modified HSA was preferentially taken up by human macrophages compared with other vascular cell types such as endothelial cells and smooth muscle cells. Conclusions: Modified89Zr-labeled HSA probes were recognized by different subsets of polarized macrophages, and maleylated HSA may be a promising radiotracer for radio-nuclide imaging of macrophage-rich inflammatory vascular diseases. © 2019 Ahmed et al.

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