Nanoparticles Direct Immune System to Scrub Atherosclerotic Plaques

The buildup of plaques within blood vessel walls is the underlying cause of strokes and heart attacks. These plaques contain many dead or dying cells that are not flushed out by the immune system fast enough.

Now, researchers from Stanford are reporting on a new drug-carrying nanoparticle that can seek out atherosclerotic plaques and stimulate white blood cells to clear out the cellular debris within. The process can reduce plaques while lowering the chances that they will destabilize and pop-off, causing strokes and other damage downstream.

The nanoparticle, which is in the shape of a tube, targets monocytes and macrophages, cells of the immune system, and uses a drug (inhibitor of the antiphagocytic CD47-SIRPα signalling axis) to motivate these cells to grab onto and digest dead and dying cells. Since the nanoparticles are attracted to atherosclerotic plaques, all this happens right where the activity is most beneficial.

Because the technology affects the interior of the immune cells, it seems to be very effective at producing well targeted effects. “We found we could stimulate the macrophages to selectively eat dead and dying cells – these inflammatory cells are precursor cells to atherosclerosis – that are part of the cause of heart attacks,” said Bryan Smith, one of the senior authors of the study, in a press release. “We could deliver a small molecule inside the macrophages to tell them to begin eating again.”


The dotted line outlines the atherosclerotic artery and the green represents the nanoparticles, which are in the plaque. The red indicates macrophages, which is the cell type that the nanoparticles are stimulating to eat the debris.

Because the technology affects the interior of the immune cells, it seems to be very effective at producing well targeted effects. “We found we could stimulate the macrophages to selectively eat dead and dying cells – these inflammatory cells are precursor cells to atherosclerosis – that are part of the cause of heart attacks,” said Bryan Smith, one of the senior authors of the study, in a press release. “We could deliver a small molecule inside the macrophages to tell them to begin eating again.”

“We were able to marry a groundbreaking finding in atherosclerosis by our collaborators with the state-of-the-art selectivity and delivery capabilities of our advanced nanomaterial platform. We demonstrated the nanomaterials were able to selectively seek out and deliver a message to the very cells needed,” Smith added. “It gives a particular energy to our future work, which will include clinical translation of these nanomaterials using large animal models and human tissue tests. We believe it is better than previous methods.”

Study in Nature Nanotechnology: Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis

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