Researchers from Denmark, the Netherlands and the US have developed a technique for creating multimodal contrast agents for the diagnosis of atherosclerosis, a disease affecting the arterial blood vessels [Cormode et al., Nano Letters (2008), doi:10.2021/nl801958b].

The transport of fats around the body is carried out by lipoproteins. In cardiovascular disease, these have been established to play a crucial role in the formation of cholesterol rich deposits in arteries, known as atherosclerotic plaques. These plaques may eventually rupture and cause clinical events such as stroke and heart attacks.

The smallest member of the lipoprotein family, High Density Lipoprotein (HDL), transports cholesterol from these plaques back to the liver and is therefore referred to as “good cholesterol”. Furthermore, its properties as a natural nanoparticle are ideally suited for modification for biomedical imaging purposes.

Willelm Mulder, from the Mount Sinai School of Medicine in New York, explains: “Having previously established a magnetic resonance imaging contrast agent platform based on HDL for plaque imaging, our team further modified this platform by taking advantage of the native design of HDL: a hydrophobic core with a lipid coating into which apolipoprotein A-I (apoA-I) is embedded.”

The researchers were able to replace the natural hydrophobic core of the HDL nanoparticles with gold, iron oxide, or quantum dot nanocrystals, for use as computed tomography, magnetic resonance, and fluorescence imaging contrast agents, respectively. By including additional labels in the corona of the particles, namely paramagnetic and fluorescent lipids, they were able to make the HDL-like nanoparticles multifunctional.

“We have demonstrated the use of this platform for multimodality imaging of macrophages in atherosclerosis”, says Mulder. “This technology will contribute to the identification of macrophage rich plaques using diagnostic imaging.” He adds that other potential applications include imaging of inflammatory diseases such as rheumatoid arthritis, and the investigation of lipoprotein metabolism.