Editors' ChoiceAtherosclerosis

iHeart nano: A sweet cure

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Science Translational Medicine  11 Mar 2015:
Vol. 7, Issue 278, pp. 278ec40
DOI: 10.1126/scitranslmed.aaa9864

Foam cells, a major contributor to atherosclerotic plaques, are formed when macrophages take up modified lipids via scavenger receptors. In search of therapeutic agents capable of targeting scavenger receptors, Lewis et al. wondered if sugar-based nanoparticles (NPs) could be modified to disrupt the uptake of these lipids. Their results show early success in limiting atherogenesis by inhibiting the contribution of scavenger receptors.

Lewis et al. identified sugar-based amphilic macromolecules with the greatest potential to bind to scavenger receptors with in silico and in vitro methods. They then attached the macromolecules to nanoparticles that could be injected into Apoe-/- atherosclerosis-prone mice to test the hypothesis in vivo. Confocal microscopy revealed that the NPs successfully accumulated in the atherosclerotic plaque–burdened vessels in the mice and caused a robust 37% reduction in artery occlusion, less lipid accumulation and inflammatory signaling, and down-regulation of scavenger receptor expression. The investigators concluded that scavenger receptor–targeted NPs can shift macrophages to a less inflammatory state and are an effective approach to preventing atherogenesis.

This study has limitations, including reliance on animal models, but was strengthened by the use of a series of translational tools to optimize the NPs.

D. R. Lewis et al., Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1424594112 (2015). [Abstract]

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