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

Abstract

Atherosclerosis (AS) is one of the leading causes of mortality in high-income countries. Early diagnosis of vulnerable atherosclerotic lesions is one of the biggest challenges currently facing cardiovascular medicine. The present study focuses on developing targeted nanoparticles (NPs) in order to improve the detection of vulnerable atherosclerotic-plaques. Various biomarkers involved in the pathogenesis of atherosclerotic-plaques have been identified and one of these promising candidates for diagnostic targeting is interleukin 10 (IL10). IL10 has been shown to be a key anti-inflammatory responding cytokine in the early stages of atherogenesis, and has already been used for therapeutic interventions in humans and mice. IL10, the targeting sequence, was coupled to two different types of NPs: protamine-oligonucleotide NPs (proticles) and sterically stabilized liposomes in order to address the question of whether the recognition and detection of atherosclerotic-lesions is primarily determined by the targeting sequence itself, or whether it depends on the NP carrier system to which the biomarker is coupled. Each IL10-targeted NP was assessed based on its sensitivity and selectivity toward characterizing atherosclerotic-plaque lesions using an apolipoprotein E-deficient mouse as the model of atherosclerosis. Aortas from apolipoprotein E-deficient mice fed a high fat diet, were stained with either fluorescence-labeled IL10 or IL10-coupled NPs. Ex vivo imaging was performed using confocal laser-scanning microscopy. We found that IL10-targeted proticles generated a stronger signal by accumulating at the surface of atherosclerotic-plaques, while IL10-targeted, sterically stabilized liposomes showed a staining pattern deeper in the plaque compared to the fluorescence-labeled IL10 alone. Our results point to a promising route for enhanced in vivo imaging using IL10-targeted NPs. NPs allow a higher payload of signal emitting molecules to be delivered to the atherosclerotic-plaques, thus improving signal detection. Importantly, this allows for the opportunity to visualize different areas within the plaque scenario, depending on the nature of the applied nanocarrier.

Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE −/− mouse model of atherosclerosis with alterations in IL10/AMPKα pathway

“…Moreover, recent studies have focused on macrophages and, in particular, promotion from pro-inflammation to pro-resolution, as a means to reduce atherogenesis and similar chronic inflammatory pathologies [23] , [24] . Indeed, the anti-inflammatory cytokine IL-10, which promotes resolution by stimulating efferocytosis and tissue repair, is now being engineered as nanoparticles to allow more specific targeting, and has resulted in the stabilization of the fibrous cap and necrotic core reduction in HFD-fed LDLR −/− mice [25] . Furthermore, a recent study by Zhu et al.…”

Cytokines: Roles in Atherosclerosis Disease Progression and Potential Therapeutic Targets

“…Although nanoparticles and micelles are capable of directing antibodies and antagonists for cell surface receptors to atherosclerotic plaques for imaging [86,87], very little has been developed for directing cytokine therapies [88]. However nanoparticles have been shown to be able to target the anti-inflammatory cytokine IL-10 and improve ex vivo imaging of plaques from AopE -/- mice [90]. This study demonstrates that it is possible to target cytokines with nanoparticles and highlight the potential to use them to deliver cytokine-targeted therapies directly to atherosclerotic plaques.…”

Protamine – A Review on an Oligonucleotide-Binding Peptide Applied in Nanopharmaceuticals including Vaccines

“…After some years, the same group published an improved IL-10 mediated targeting strategy. They noticed differences in distribution between Proticles and targeted liposomes in mice ex-vivo (Almer et al 2014). Recently, secretoneurin was incorporated in Proticles by co-assembling like already mentioned above.…”