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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

Plaque detection in apoE−/− mouse model.(A) Representative magnetic resonance images obtain before (0 h) and after (24 h, 48 h) the injection of each type of nanoparticles. The white arrows point at slightly darker areas with respect to the pre-injection images in the case of apoE−/− mice injected with NP-CD163(m). (B) Graph showing the normalized mean value of the abdominal aortic wall for apoE−/− and wild type mice injected with either NP-CD163(m) or NP-IgG(m) at 0, 24 and 48 hours. The error bars represent the SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 versus apoE + NP-CD163 t = 48h.
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f3: Plaque detection in apoE−/− mouse model.(A) Representative magnetic resonance images obtain before (0 h) and after (24 h, 48 h) the injection of each type of nanoparticles. The white arrows point at slightly darker areas with respect to the pre-injection images in the case of apoE−/− mice injected with NP-CD163(m). (B) Graph showing the normalized mean value of the abdominal aortic wall for apoE−/− and wild type mice injected with either NP-CD163(m) or NP-IgG(m) at 0, 24 and 48 hours. The error bars represent the SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 versus apoE + NP-CD163 t = 48h.

Mentions: ApoE−/− and wild type mice were both injected in separate experiments with either NP-CD163(m) or NP-IgG(m) and the pararenal abdominal aorta was imaged at four time points: before the injection and at 1, 24 and 48 hours post-injection. No differences were seen at 1hour post-injection (data not shown), but a signal decrease in the aortic wall was observed in apoE−/− mice injected with NP-CD163 (n = 9) over time with respect to the pre-injection signal. At 24 hours there was a signal decrease that became significant at 48 hours after the injection (p < 0.01). Conversely, when the same type of mice were injected with the control probe NP-IgG(m) there were not significant signal variations over time or in healthy mice (See Supplementary tables S7-S9 for statistical details). Likewise, the wall signal intensity did not vary compared to pre-injection signal in the case of wild type mice injected with either NP-CD163(m) or NP-IgG(m) (Fig. 3).


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)

Plaque detection in apoE−/− mouse model.(A) Representative magnetic resonance images obtain before (0 h) and after (24 h, 48 h) the injection of each type of nanoparticles. The white arrows point at slightly darker areas with respect to the pre-injection images in the case of apoE−/− mice injected with NP-CD163(m). (B) Graph showing the normalized mean value of the abdominal aortic wall for apoE−/− and wild type mice injected with either NP-CD163(m) or NP-IgG(m) at 0, 24 and 48 hours. The error bars represent the SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 versus apoE + NP-CD163 t = 48h.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Plaque detection in apoE−/− mouse model.(A) Representative magnetic resonance images obtain before (0 h) and after (24 h, 48 h) the injection of each type of nanoparticles. The white arrows point at slightly darker areas with respect to the pre-injection images in the case of apoE−/− mice injected with NP-CD163(m). (B) Graph showing the normalized mean value of the abdominal aortic wall for apoE−/− and wild type mice injected with either NP-CD163(m) or NP-IgG(m) at 0, 24 and 48 hours. The error bars represent the SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 versus apoE + NP-CD163 t = 48h.
Mentions: ApoE−/− and wild type mice were both injected in separate experiments with either NP-CD163(m) or NP-IgG(m) and the pararenal abdominal aorta was imaged at four time points: before the injection and at 1, 24 and 48 hours post-injection. No differences were seen at 1hour post-injection (data not shown), but a signal decrease in the aortic wall was observed in apoE−/− mice injected with NP-CD163 (n = 9) over time with respect to the pre-injection signal. At 24 hours there was a signal decrease that became significant at 48 hours after the injection (p < 0.01). Conversely, when the same type of mice were injected with the control probe NP-IgG(m) there were not significant signal variations over time or in healthy mice (See Supplementary tables S7-S9 for statistical details). Likewise, the wall signal intensity did not vary compared to pre-injection signal in the case of wild type mice injected with either NP-CD163(m) or NP-IgG(m) (Fig. 3).

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