The biological properties of iron oxide core high-density lipoprotein in experimental atherosclerosis

Abstract

Lipoproteins are a family of plasma nanoparticles responsible for the transportation of lipids throughout the body. High-density lipoprotein (HDL), the smallest of the lipoprotein family, measures 7–13 nm in diameter and consists of a cholesteryl ester and triglyceride core that is covered with a monolayer of phospholipids and apolipoproteins. We have developed an iron oxide core HDL nanoparticle (FeO-HDL), which has a lipid based fluorophore incorporated in the phospholipid layer. This nanoparticle provides contrast for optical imaging, magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Consequently, FeO-HDL can be visualized on the anatomical, cellular and sub-cellular level. In the current study we show that the biophysical features of FeO-HDL closely resemble those of native HDL and that FeO-HDL possess the ability to mimic HDL characteristics both in vitro as well as in vivo. We demonstrate that FeO-HDL can be applied to image HDL interactions and to investigate disease settings where HDL plays a key function. More generally, we have demonstrated a multimodal approach to study the behavior of biomaterials in vitro as well as in vivo. The approach allowed us to study nanoparticle dynamics in circulation, as well as nanoparticle targeting and uptake by tissues and cells of interest. Moreover, we were able to qualitatively assess nanoparticle excretion, critical for translating nanotechnologies to the clinic.

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

“…Other studies have incorporated solid nanoparticles of gold, iron oxide, and quantum dots with apoA-I and lipid shells in order to achieve multifunctional imaging of atherosclerotic plaques. 17,18 Fewer papers have explored the localization of reconstituted HDL in the liver. Sriram et al modified apoA-I protein with Gd [MTS-ADO3A] labeling, and found increases in MRI signals in the liver as well as in the kidney.…”

Synthesis and Characterization of Functionalized Magnetic Nanoparticles for the Detection of Pesticide

“…Nanoscale magnetic particles have attracted much attention because they are able to be transported to targeted locations [1][2][3][4] by means of an external magnetic field as well as to be used for data storage [5] and magnetic resonance imaging [6,7].…”

Anti-inflammatory mediators for molecular imaging of atherosclerosis

“…Over the last decade, the method for lipoprotein inspired imaging of AS by producing fully synthetic HDL-particles containing a spherical nanocrystalline core was established (41,42). In synthetic HDLs the inner lipophilic core is surrounded by a monolayer of phospholipids with apo-AI molecules associated to the surface.…”

“…In synthetic HDLs the inner lipophilic core is surrounded by a monolayer of phospholipids with apo-AI molecules associated to the surface. The nanocrystalline core can be composed of either Gold-nanoparticles for computed tomography (CT) imaging, quantum dots (QD) for optical imaging (41) or ironoxide-nanoparticles for magnet resonance imaging (MRI) (42). Additionally, fluorescent dyes or phospholipid anchored Gadolinium (Gd)-chelates can be incorporated into the outer phospholipid monolayer of synthetic HDLs to construct a multimodal signal-emitting particle for molecular imaging.…”