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Ahmed, M., Baumgartner, R., Aldi, S., Dusart, P., Hedin, U., Gustafsson, B. & Caidahl, K. (2019). Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors. International Journal of Nanomedicine, 14, 3723-3741
Open this publication in new window or tab >>Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
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2019 (English)In: International Journal of Nanomedicine, ISSN 1176-9114, E-ISSN 1178-2013, Vol. 14, p. 3723-3741Article in journal (Refereed) Published
Abstract [en]

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 (Zr-89) 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-Al, 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-Al (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: Modified Zr-89-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.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:kth:diva-253000 (URN)10.2147/IJN.S197990 (DOI)000469112300001 ()
Note

QC 20190619

Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved
Ahmed, M., Gustafsson, B., Aldi, S., Dusart, P., Egri, G., Butler, L. M., . . . Caidahl, K. (2019). Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting. Cellular and Molecular Bioengineering, 12(1), 15-32
Open this publication in new window or tab >>Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting
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2019 (English)In: Cellular and Molecular Bioengineering, ISSN 1865-5025, E-ISSN 1865-5033, Vol. 12, no 1, p. 15-32Article in journal (Refereed) Published
Abstract [en]

Introduction: Inflammation is an important risk-associated component of many diseases and can be diagnosed by molecular imaging of specific molecules. The aim of this study was to evaluate the possibility of targeting adhesion molecules on inflammation-activated endothelial cells and macrophages using an innovative multimodal polyvinyl alcohol-based microbubble (MB) contrast agent developed for diagnostic use in ultrasound, magnetic resonance, and nuclear imaging. Methods: We assessed the binding efficiency of antibody-conjugated multimodal contrast to inflamed murine or human endothelial cells (ECs), and to peritoneal macrophages isolated from rats with peritonitis, utilizing the fluorescence characteristics of the MBs. Single-photon emission tomography (SPECT) was used to illustrate 99m Tc-labeled MB targeting and distribution in an experimental in vivo model of inflammation. Results: Flow cytometry and confocal microscopy showed that binding of antibody-targeted MBs to the adhesion molecules ICAM-1, VCAM-1, or E-selectin, expressed on cytokine-stimulated ECs, was up to sixfold higher for human and 12-fold higher for mouse ECs, compared with that of non-targeted MBs. Under flow conditions, both VCAM-1- and E-selectin-targeted MBs adhered more firmly to stimulated human ECs than to untreated cells, while VCAM-1-targeted MBs adhered best to stimulated murine ECs. SPECT imaging showed an approximate doubling of signal intensity from the abdomen of rats with peritonitis, compared with healthy controls, after injection of anti-ICAM-1-MBs. Conclusions: This novel multilayer contrast agent can specifically target adhesion molecules expressed as a result of inflammatory stimuli in vitro, and has potential for use in disease-specific multimodal diagnostics in vivo using antibodies against targets of interest.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Antibodies, Contrast agent, Confocal microscopy, Endothelial cells, Flow cytometry, Inflammation, In vitro, In vivo, Macrophages, Polyvinyl-alcohol
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:kth:diva-243933 (URN)10.1007/s12195-018-00562-z (DOI)000456651000002 ()2-s2.0-85057585819 (Scopus ID)
Note

QC 20190313

Available from: 2019-03-13 Created: 2019-03-13 Last updated: 2019-03-13Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2747-3214

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