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Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI.

Tarin C, Carril M, Martin-Ventura JL, Markuerkiaga I, Padro D, Llamas-Granda P, Moreno JA, García I, Genicio N, Plaza-Garcia S, Blanco-Colio LM, Penades S, Egido J - Sci Rep (2015)

Bottom Line: We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI.Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI.The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Patología Vascular y Renal. IIS Fundación Jiménez Díaz, Universidad Autónoma. Av. Reyes Católicos 2, 28040, Madrid, Spain.

ABSTRACT
CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (-) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesions.

No MeSH data available.


Related in: MedlinePlus

Validation of the plaque presence and molecular biomarkers in apoE−/− mice.Representative micrographs of aortic serial sections isolated from apoE−/− NP CD163(m) injected mice. (A) Vascular smooth muscle staining by α-actin immunohistochemistry detection, (B) Lipid determination by Oil red staining (C) CD68 immunohistochemistry detection and (D) CD163 immunohistochemistry detection. (n = 7).
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f4: Validation of the plaque presence and molecular biomarkers in apoE−/− mice.Representative micrographs of aortic serial sections isolated from apoE−/− NP CD163(m) injected mice. (A) Vascular smooth muscle staining by α-actin immunohistochemistry detection, (B) Lipid determination by Oil red staining (C) CD68 immunohistochemistry detection and (D) CD163 immunohistochemistry detection. (n = 7).

Mentions: The histology of the apoE−/− aortas, harvested after MRI scan, showed that all the mice had atherosclerotic lesions in the MRI scanned area (Fig. 4) with an average size of 50,000 ± 14,000 μm2. The plaques in the aortic wall were composed by a layer of smooth muscle cells (Fig. 4A) with small lipid deposits (oil red staining, Fig. 4B) and with the presence of infiltrated macrophages (CD68, Fig. 4C). MRI results were confirmed in the atherosclerotic mice samples by CD163 (Fig. 4D), and CD68 staining. The incubation with an isotype-matched immunoglobulin was used as a negative control, showing the specificity of the immunohistochemistry (Supplemental Figure S6).


Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI.

Tarin C, Carril M, Martin-Ventura JL, Markuerkiaga I, Padro D, Llamas-Granda P, Moreno JA, García I, Genicio N, Plaza-Garcia S, Blanco-Colio LM, Penades S, Egido J - Sci Rep (2015)

Validation of the plaque presence and molecular biomarkers in apoE−/− mice.Representative micrographs of aortic serial sections isolated from apoE−/− NP CD163(m) injected mice. (A) Vascular smooth muscle staining by α-actin immunohistochemistry detection, (B) Lipid determination by Oil red staining (C) CD68 immunohistochemistry detection and (D) CD163 immunohistochemistry detection. (n = 7).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663748&req=5

f4: Validation of the plaque presence and molecular biomarkers in apoE−/− mice.Representative micrographs of aortic serial sections isolated from apoE−/− NP CD163(m) injected mice. (A) Vascular smooth muscle staining by α-actin immunohistochemistry detection, (B) Lipid determination by Oil red staining (C) CD68 immunohistochemistry detection and (D) CD163 immunohistochemistry detection. (n = 7).
Mentions: The histology of the apoE−/− aortas, harvested after MRI scan, showed that all the mice had atherosclerotic lesions in the MRI scanned area (Fig. 4) with an average size of 50,000 ± 14,000 μm2. The plaques in the aortic wall were composed by a layer of smooth muscle cells (Fig. 4A) with small lipid deposits (oil red staining, Fig. 4B) and with the presence of infiltrated macrophages (CD68, Fig. 4C). MRI results were confirmed in the atherosclerotic mice samples by CD163 (Fig. 4D), and CD68 staining. The incubation with an isotype-matched immunoglobulin was used as a negative control, showing the specificity of the immunohistochemistry (Supplemental Figure S6).

Bottom Line: We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI.Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI.The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de Patología Vascular y Renal. IIS Fundación Jiménez Díaz, Universidad Autónoma. Av. Reyes Católicos 2, 28040, Madrid, Spain.

ABSTRACT
CD163 is a membrane receptor expressed by macrophage lineage. Studies performed in atherosclerosis have shown that CD163 expression is increased at inflammatory sites, pointing at the presence of intraplaque hemorrhagic sites or asymptomatic plaques. Hence, imaging of CD163 expressing macrophages is an interesting strategy in order to detect atherosclerotic plaques. We have prepared a targeted probe based on gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody for the specific detection of CD163 by MRI. Firstly, the specificity of the targeted probe was validated in vitro by incubation of the probe with CD163(+) or (-) macrophages. The probe was able to selectively detect CD163(+) macrophages both in human and murine cells. Subsequently, the targeted probe was injected in 16 weeks old apoE deficient mice developing atherosclerotic lesions and the pararenal abdominal aorta was imaged by MRI. The accumulation of probe in the site of interest increased over time and the signal intensity decreased significantly 48 hours after the injection. Hence, we have developed a highly sensitive targeted probe capable of detecting CD163-expressing macrophages that could provide useful information about the state of the atheromatous lesions.

No MeSH data available.


Related in: MedlinePlus