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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)