Templated high density lipoprotein nanoparticles as potential therapies and for molecular delivery.

High density lipoproteins (HDLs) are dynamic natural nanoparticles best known for their role in cholesterol transport and the inverse correlation that exists between blood HDL levels and the risk of developing coronary heart disease. In addition, enhanced HDL-cholesterol uptake has been demonstrated in several human cancers. As such, the use of HDL as a therapeutic and as a vehicle for systemic delivery of drugs and as imaging agents is increasingly important. HDLs exist on a continuum from the secreted HDL-scaffolding protein, apolipoprotein A-1 (Apo A1), to complex, spherical "mature" HDLs. Aspects of HDL particles including their size, shape, and surface chemical composition are being recognized as critical to their diverse biological functions. Here we review HDL biology; strategies for synthesizing HDLs; data supporting the clinical use and benefit of directly administered HDL; a rationale for developing synthetic methods for spherical, mature HDLs; and, the potential to employ HDLs as therapies, imaging agents, and drug delivery vehicles. Importantly, methods that utilize nanoparticle templates to control synthetic HDL size, shape, and surface chemistry are highlighted.