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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2013

AutorInnen: Almer, G; Frascione, D; Pali-Schöll, I; Vonach, C; Lukschal, A; Stremnitzer, C; Diesner, SC; Jensen-Jarolim, E; Prassl, R; Mangge, H

Titel: Interleukin-10: an anti-inflammatory marker to target atherosclerotic lesions via PEGylated liposomes.

Quelle: Mol Pharm. 2013; 10(1):175-186



Autor/innen der Vetmeduni Vienna:

Jensen-Jarolim Erika
Pali Isabella

Beteiligte Vetmed-Organisationseinheiten
Messerli Forschungsinstitut, Abteilung für Komparative Medizin


Abstract:
Atherosclerosis (AS) causes cardiovascular disease, which leads to fatal clinical end points like myocardial infarction or stroke, the most prevalent causes of death in developed countries. An early, noninvasive method of detection and diagnosis of atherosclerotic lesions is necessary to prevent and treat these clinical end points. Working toward this goal, we examined recombinant interleukin-10 (IL-10), stealth liposomes with nanocargo potency for NMRI relevant contrast agents, and IL-10 coupled to stealth liposomes in an ApoE-deficient mouse model using confocal laser-scanning microscopy (CLSM). Through ex vivo incubation and imaging with CLSM, we showed that fluorescently labeled IL-10 is internalized by AS plaques, and a low signal is detected in both the less injured aortic surfaces and the arteries of wild-type mice. In vivo experiments included intravenous injections of (i) fluorescent IL-10, (ii) IL-10 targeted carboxyfluorescin (CF-) labeled stealth liposomes, and (iii) untargeted CF-labeled stealth liposomes. Twenty-four hours after injection the arteries were dissected and imaged ex vivo. Compared to free IL-10, we observed a markedly stronger fluorescence intensity with IL-10 targeted liposomes at AS plaque regions. Moreover, untargeted CF-labeled liposomes showed only weak, unspecific binding. Neither free IL-10 nor IL-10 targeted liposomes showed significant immune reaction when injected into wild-type mice. Thus, the combined use of specific anti-inflammatory proteins, high payloads of contrast agents, and liposome particles should enable current imaging techniques to better recognize and visualize AS plaques for research and prospective therapeutic strategies.

Keywords Pubmed: Animals
Anti-Inflammatory Agents/metabolism
Apolipoproteins E/metabolism
Arteries/metabolism
Atherosclerosis/diagnosis*
Atherosclerosis/metabolism
Biological Markers/metabolism
Contrast Media/administration & dosage
Contrast Media/chemistry
Cytokines/metabolism
Drug Delivery Systems
Female
Interleukin-10/metabolism*
Liposomes/administration & dosage*
Liposomes/chemistry
Liposomes/pharmacokinetics
Magnetic Resonance Imaging/methods
Mice
Mice, Inbred BALB C
Microscopy, Confocal/methods
Plaque, Atherosclerotic/diagnosis*
Plaque, Atherosclerotic/metabolism
Polyethylene Glycols/administration & dosage
Polyethylene Glycols/chemistry
Recombinant Fusion Proteins/administration & dosage
Spleen/drug effects
Spleen/metabolism


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