Good news!
"A new generation of “theranostic” nanoparticles has been shown to both detect and reduce plaques in the arteries. Nanoparticles absorbed by immune cells in the arteries, where they work to lower inflammation and draw out harmful cholesterol, offer an entirely new way of not just diagnosing but fighting heart disease without drugs. ..."
"... The study used advanced imaging techniques to track the movement of the nanoparticles in pre-clinical models of heart disease. They were able to target inflamed plaques and significantly reduce both plaque size and inflammation.
"One of the key challenges in treating atherosclerosis is that inflammation fuels plaque build-up, creating a vicious cycle. Our nanoparticles help break that cycle, which could lead to better long-term outcomes for patients,” ...
In addition to their ability to shrink plaques, the nanoparticles have powerful imaging capabilities that allow for earlier detection of arterial disease. This could help cardiologists identify at-risk patients sooner and intervene with treatments before complications arise. ..."
From the highlights and abstract:
"Highlights
• Atherosclerosis is the deposition of fatty plaques in arteries and the main cause of heart attacks.
• Strategies to improve detection and reduce atherosclerotic plaques are needed.
• Multifunctional porphyrin-lipid nanoparticles (Por-NPs) have diagnostic and therapeutic properties.
• Por-NPs are internalized by macrophages and track to atherosclerotic plaques, visualized using multiple imaging modalities.
• Por-NPs exert atheroprotective effects in vitro in macrophages. They suppress inflammation and promote cholesterol efflux.
• Por-NPs exhibit therapeutic effects in two murine models of atherosclerosis and significantly reduce plaque size.
Abstract
Background
Porphyrin-lipid nanoparticles (Por-NPs) have unrealized potential for atherosclerosis. Por-NPs incorporate porphyrin-lipid which permits fluorescence imaging and chelates Copper-64 (64Cu) for positron emission tomography (PET) imaging. Their outer shell contains a short peptide ‘R4F’ that enables macrophage targeting and therapeutic effects. Accordingly, this study investigates the simultaneous diagnostic and therapeutic properties of Por-NPs in atherosclerosis.
Results
In vitro, Por-NPs were found to be internalized by immortalised bone marrow-derived macrophages (iBMDMs), visualized via fluorescence microscopy and flow cytometry.
Por-NPs also increased cholesterol efflux from [3H]-cholesterol-loaded iBMDMs, (49 %, P < 0.05).
Incubation of iBMDMs with Por-NPs reduced mRNA levels of inflammatory mediators Il1b (88 %), Il18 (54 %) Ccl5 (75 %) and Ccl17 (92 %), and protein secretion of IL-1β (69 %), CCL5 (82 %) and CCL17 (94 %), P < 0.05. Por-NPs suppressed inflammasome components Nlrp3 (69 %) and Asc (36 %), P < 0.05. Studies using siRNA deletion of SR-B1 and methyl-β-cyclodextrin, revealed the anti-inflammatory properties of Por-NPs were independent of SR-B1 and cholesterol efflux. However, Por-NPs suppressed activation of inflammatory transcription factor NF-κB (53 %, P < 0.05).
In vivo, in Apoe−/− mice, serial non-invasive PET imaging showed 64Cu-labelled Por-NPs localised in hearts and detected increases in plaque size longitudinally with high-cholesterol diet. Por-NP fluorescence was visualized in aortic sinus plaques, co-localised with CD68+ macrophages, and by fluorescence IVIS imaging in aortic arch plaque.
In two murine models, Por-NP-treated mice had smaller early-stage (22 %) and unstable plaques (52 %). Por-NP-treated mice had fewer circulating (32 %) and aortic (81 %) monocytes, and lower mRNA levels of aortic arch Rela (26 %) and Nfkb1 (27 %), P < 0.05.
Conclusions
Por-NPs detect plaques using multiple imaging modalities and exhibit atheroprotective effects, presenting as novel nanoscale theranostics for atherosclerosis."
Nanoparticles engineered to suck the plaque out of arteries (original news release) "Researchers at SAHMRI are using specially designed nanoparticles to detect and help treat plaque build-up in arteries for the first time, offering a potential new approach to diagnosing and managing heart disease."
Theranostic porphyrin nanoparticles identify atherosclerosis via multimodal imaging and elicit atheroprotective effects (open access)
Graphical abstract
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