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Supramolecular Assembly of High-Density Lipoprotein Mimetic Nanoparticles Using Lipid-Conjugated Core Scaffolds

Author:
Henrich, Stephen E., Hong, Bong Jin, Rink, Jonathan S., Nguyen, SonBinh T., Thaxton, C. Shad
Source:
Journal of the American Chemical Society 2019 v.141 no.25 pp. 9753-9757
ISSN:
1520-5126
Subject:
cholesterol, enzyme activity, geometry, hepatocytes, high density lipoprotein, inflammation, macrophages, nanoparticles, phospholipids, protein secondary structure, therapeutics
Abstract:
Synthetic high-density lipoprotein (HDL) mimics have emerged as promising therapeutic agents. However, approaches to date have been unable to reproduce key features of spherical HDLs, which are the most abundant human HDL species. Here, we report the synthesis and characterization of spherical HDL mimics using lipid-conjugated organic core scaffolds. The core design motif constrains and orients phospholipid geometry to facilitate the assembly of soft-core nanoparticles that are approximately 10 nm in diameter and resemble human HDLs in their size, shape, surface chemistry, composition, and protein secondary structure. These particles execute salient HDL functions, including efflux of cholesterol from macrophages, cholesterol delivery to hepatocytes, support lecithin:cholesterol acyltransferase activity, and suppress inflammation. These results represent a significant step toward a genuine functional mimic of human HDLs.
Agid:
6481365