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.

Development of111In-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging

“…Also, it is well known that macrophages are predisposed to phagocytize particles such as liposomes (16,17), and several liposome-based imaging probes have been reported recently (27,28). Therefore, in this study, we used liposomes as carriers for the atherosclerotic region and designed a SPECT imaging probe.…”

Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

“…We have previously shown that Atto655-IL10 penetrates deep into the plaques when liposomes were the nanocarrier 12 (see also in Figure 5A and B). Upon switching the NP to IL10-coated proticles and comparing all formulations, we observed a different staining pattern where the signal originated more on the surface of the atherosclerotic-plaques ( Figure 5C) and strongly co-localized with the endothelium ( Figure 2D) and partially with CD68-positive macrophages on the plaque surface ( Figure 3D).…”

“…8 It plays a key role in counter-regulating the immune and inflammatory responses in AS pathogenesis by inhibiting the production of pro-inflammatory cytokines and mediators from macrophages and dendritic cells. [9][10][11][12] The comparatively high amounts of IL10 found in atherosclerotic-plaques make it diagnostically relevant. 13,14 IL10 is produced by a variety of sources which include, but are not limited to, T-helper cells, 15 monocytes, macrophages, 9 epithelial cells, and tumor cells.…”

Atherosclerotic disease and management challenges with nanomedicine: EU FP7 NMP funded “NanoAthero” and “CosmoPHOS-nano” large-scale projects

“…Although nanoparticle-based therapy is becoming more and more common in oncology, no specific nanoparticle-based system has yet been approved for diagnosis or therapy in cardiovascular diseases (8)(9)(10)(11)(12). Indeed, integrating a transport mechanism, a stealth coating, targeting and an active molecule into one and the same nanosystem (known as a third-generation nanosystem) has not yet been clinically validated in the field of atherosclerosis.…”