High-Density Lipoprotein-like Magnetic Nanostructures (HDL-MNS): Theranostic Agents for Cardiovascular Disease

Abstract

We report the development of potential theranostic agents for cardiovascular disease that are based on high-density lipoprotein-like magnetic nanostructures (HDL-MNS). The HDL-MNS offer prospects for diagnosis via noninvasive magnetic resonance imaging for anatomic detection and also serve as effective cholesterol efflux agents to address atherosclerotic vascular lesions. The HDL-MNS are synthesized by adding phospholipids and the HDL-defining apolipoprotein A1 to the surface of magnetic nanostructures (MNS) to mimic some aspects of natural HDL particles. From a diagnostic perspective, HDL-MNS show a 5 times higher contrast (r2 relaxivity up to 383 mM–1 s–1) in magnetic resonance imaging (MRI) than commercially available T2 MRI contrast agents (e.g., Ferumoxytol). Internalization of HDL-MNS by macrophage cells was confirmed by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), inductive-coupled plasma mass spectrometry (ICP-MS), and successfully imaged via MRI. Also, the HDL-MNS particles show capacity to induce cholesterol efflux (∼4.8%) from macrophage cells comparable to natural HDL (∼4.7%), providing a pathway to prevent and treat cardiovascular disease via reverse cholesterol transport. The ability to image macrophage cells that have internalized HDL-MNS along with the cholesterol efflux capacity demonstrates the potential of the HDL-MNS particles as theranostic agents.