title: Interleukin-10: an anti-inflammatory marker to target atherosclerotic lesions via PEGylated liposomes.
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.
authors.affiliation: Institute of Biophysics and Nanosystems Research, Austrian Academy of Science, Graz, Austria.
authors.forename: Gunter
authors.initials: G
authors.lastname: Almer
authors.forename: Daniela
authors.initials: D
authors.lastname: Frascione
authors.forename: Isabella
authors.initials: I
authors.lastname: Pali-Schöll
authors.forename: Caroline
authors.initials: C
authors.lastname: Vonach
authors.forename: Anna
authors.initials: A
authors.lastname: Lukschal
authors.forename: Caroline
authors.initials: C
authors.lastname: Stremnitzer
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Diesner
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
authors.forename: Ruth
authors.initials: R
authors.lastname: Prassl
authors.forename: Harald
authors.initials: H
authors.lastname: Mangge
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001158:Arteries / Q000378:metabolism; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D015415:Biomarkers; D003287:Contrast Media; D016207:Cytokines; C556062:IL10 protein, mouse; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D011092:Polyethylene Glycols