Medizinische Universität Graz - Research portal
Selected Publication:
Almer, G.
Targeting and image enhancement of atherosclerotic lesions with nanoparticle conjugated biomarkers in mice
[ Dissertation ] Universität Graz; 2011. pp.163.
FullText
- Authors Med Uni Graz:
- Almer Gunter
- Advisor:
- Mangge Harald
- Prassl Ruth
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- Abstract:
- In my thesis different biomarkers (BM) were evaluated for the recognition of atherosclerotic (AS-)lesions. BMs which are known to be involved in the AS-scenario were examined for targeting AS-plaques applied in a mouse model of AS. Afterwards positively selected BMs were coupled to characterized nanoparticles (NPs) for imaging to achieve an enhancement of the staining signal. Primarily confocal laser-scanning microscopy was used to visualize the aortic surface, AS-lesions and the targeting signals from the fluorescence labeled nanoconstructs ex vivo. An antibody (Ab) against the receptor for oxidized low density lipoprotein (oxLDL), LOX-1 was labeled with a fluorescence dye and successfully applied for ex vivo plaque targeting on aortic sections. The Ab was further coupled to fluorescence labeled Stealth liposomes, which resulted in a signal enhancement at the targeted plaque area. The second BM, adiponectin, normally circulates in high concentrations in different isomers in the blood. We could show that especially the globular domain of adiponectin (gAd) accumulated in acetylated LDL-injured endothelial cells and in the fibrous cap area of AS-plaques. Coupling of gAd to fluorescence labeled NPs resulted in the enhancement of the fluorescence when gAd was coupled to liposomes, respectively in an alteration of the signal pattern to a more macrophage-affine staining when coupled to protamine-oligonucleotide based particles, called proticles. The third BM, Interleukin (IL)-10, is known to possess mainly anti-inflammatory characteristics. We could show that IL-10 binds to AS-plaques but, in contrast to gAd, it penetrated deeper into the tissue and was found to be internalized by some CD68 negative foam cells. Summarized all three of the examined BMs are very promising molecules for further evaluations focussing on in vivo imaging of AS and, due to their long half life in the circulation, Stealth liposomes seem to be the NPs of choice for imaging enhancement strategies.