High-density lipoproteins (HDL) are dynamic nanoparticles that circulate in the blood and transport cholesterol. Clinically, elevated HDL levels are associated with reduced risk of atherosclerotic cardiovascular disease (ASCVD).  At the cellular level, HDLs is known to remove cholesterol from macrophages and deliver it to hepatocytes, which leads to reduced inflammation and atherosclerotic burden.  Due to the beneficial association between HDL and ASCVD, the cell-specific targeting properties of HDL, and the intrigue of using HDLs for targeted drug delivery, tremendous effort has focused on synthesizing HDLs that resemble their natural counterparts.  However, approaches to date have not reproduce key features of spherical HDLs, which are the most abundant human HDL species.<br/><br/>This presentation reports the synthesis of robust, spherical HDL mimics using lipid-conjugated organic cores.  The core design motif constrains and orients phospholipid geometry to facilitate the assembly of 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, deliver of cholesterol to hepatocytes, support lecithin:cholesterol acyltransferase activity, and suppress inflammation. These results represent a significant step toward a genuine functional mimic of human HDLs.

Organic-cored, high-density lipoprotein-mimetic nanoparticles as cholesterol transporters

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.