Trojan Horse Nanoparticles Decimate Atherosclerotic Plaque

A new study shows how carbon nanotubes loaded with a chemical inhibitor can be used to reactivate phagocytosis of apoptotic cells in the necrotic plaque core.

Researchers at Stanford University School of Medicine (SUSM; CA, USA), Michigan State University (MSU; East Lansing, USA), and other institutions have developed a new nanotherapy based on single-walled carbon nanotubes loaded with an inhibitor of the antiphagocytic CD47-SIRPα signaling axis. The macrophage-specific nanotubes accumulate within the atherosclerotic plaque, reactivate lesional phagocytosis and reducing the plaque burden by stimulating macrophages to engulf and eat cellular debris in the plaque core. By reinvigorating the macrophages, plaque size is reduced and stabilized.

In a study of the new nanotherapy in atheroprone apolipoprotein-E-deficient mice, single-cell RNA sequencing analysis revealed that the prophagocytic single-walled carbon nanotubes decrease the expression of inflammatory genes linked to cytokine and chemokine pathways in lesional macrophages. The result is a reduced, stabilized plaque. According to the researchers, the discovery could provide a potential treatment for atherosclerosis, a leading cause of death worldwide. The study was published on January 27, 2020, in Nature Nanotechnology.

“We found we could stimulate the macrophages to selectively eat dead and dying cells that are part of the cause of heart attacks. We could deliver a small molecule inside the macrophages to tell them to begin eating again,” said senior author Bryan Ronain Smith, PhD, of SUSM. “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.”

Atherosclerosis is a chronic cardiovascular disease characterized by inflammation and the gradual buildup of lipid-rich plaque in the intima of the arterial walls. Early atherosclerosis is initiated as lipid-carrying low-density lipoproteins (LDLs) get retained beneath the endothelial cells of the vessels. As the LDLs are oxidized, the endothelial cells trigger an immune response by attracting macrophages. The ingested oxidized LDLs in the macrophages increase abnormally, transforming them into foam cells that eventually rupture, causing local damage to the endothelial cells.

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Stanford University School of Medicine
Michigan State University