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Friday, 31 January 2020

Researchers have developed a nanoparticle to eat away plaque in the arteries


A new nanoparticle acting as a “Trojan Horse” makes it possible to target and literally gnaw at portions of arterial plaques of atheroma often responsible for heart attacks. This discovery may well be a potential future treatment for atherosclerosis, a disease that kills many people around the world.

How does it work? The nanoparticle is housed on the atherosclerotic plate because of its high selectivity for a specific type of immune cell: monocytes and macrophages.



The team designed these nano particles that could specifically target the atherosclerotic plaques clogging up the heart arteries. The nano particles are microscopic carbon tubules, the team explained. These tubules contain a special drug called the SHP1 inhibitor.

These plaques normally are made up of platelets and cholesterol deposits and are teeming with immune cells. These nano particles are taught to target monocytes and macrophages, which are immune cells commonly found in the plaques. These smart particles then reach within the plaques and take with them the drug agent SPH1 inhibitor. This agent then stimulates the immune cells so that they break down and engulf the broken pieces of the plaques. Thus, the arteries are cleared of the plaques with the nanocarriers carrying in the plaque busting drugs. The plaque size could be reduced remarkably say the researchers and this could reduce the risk of heart attacks that is one of the leading killers around the world.



Within the macrophases inside the plaques, there is a signalling pathway called the SHP1 pathway/ This pathway normally prevents the cells from eating up dead cells or debris or apoptosis. These debris are created within the cores of the plaques, wrote the researchers. If the signalling pathway is blocked, the macrophages go on a killing and engulfing spree and thus clear the debris left by the broken plaques.

A typical feature of an atherosclerotic plaque, wrote the researchers is accumulation of the dead cells and debris within the core of the plaque. This becomes then the “necrotic core”. If the necrotic core is not cleared, the plaque rupture can clog the arteries and lead to the heart attack says the researchers. At present there are therapies that could clear the apoptotic cells. However these therapies could also harm the healthy cells around the plaque. This novel method of nanoparticle carrier delivery of the drugs with the core thus could help protect the surrounding healthy cells and work specifically within the core.

The white dotted line describes the atherosclerotic artery and the green areas represent the nanoparticles found in the plate. Red indicates macrophages (the type of cells that nanoparticles stimulate). Credit: Michigan State

Previous studies had already made it possible to act on the surface of cells, but this new approach works intracellularly and has proven effective in stimulating macrophages.

"We have discovered that we can stimulate macrophages to selectively kill dead and dying cells (these inflammatory cells are precursors to atherosclerosis) which are common causes of heart attack," says Smith. "We could deliver a small molecule inside the macrophages to 'order' them to start eliminating said cells again," he adds.

According to Smith, this approach would also have applications beyond atherosclerosis: “We were able to marry a revolutionary discovery concerning atherosclerosis, with the cutting edge selectivity and delivery capabilities of our advanced nanomaterials platform. We have shown that nanomaterials are able to selectively search and send a message to the necessary cells ,” he said. “This gives particular energy to our future work, which will include clinical trials with these nanomaterials, using large animal models and human tissue tests. We think it will be more beneficial than the previous methods,” he added.




Bibliography:

Article: Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis

Alyssa M. Flores, Niloufar Hosseini-Nassab, Kai-Uwe Jarr, Jianqin Ye, Xingjun Zhu, Robert Wirka, Ai Leen Koh, Pavlos Tsantilas, Ying Wang, Vivek Nanda, Yoko Kojima, Yitian Zeng, Mozhgan Lotfi, Robert Sinclair, Irving L. Weissman, Erik Ingelsson, Bryan Ronain Smith & Nicholas J. Leeper

Nature Nanotechnology (2020)

https://doi.org/10.1038/s41565-019-0619-3

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