Mount Sinai Medical School Technology: An HDL-like Nanoplaform to Detect Heart Attack and Stroke

Drs. Zahi A. Fayad, Edward A. Fisher, and Kevin J. Williams are using naturally occurring lipoproteins in the body nanoplatform to predict and prevent cardiovascular disease. Lipoproteins are protein-lipid particles which circulate in the blood transporting lipids such as cholesterol and triglycerides. One such lipoprotein nanoparticle is called high-density lipoproteins (HDL) and is often regarded as "good cholesterol" due to its ability to remove excess plaque-forming cholesterol from artery walls and transporting it to the liver for removal. Fayad, Fisher, and Williams are working toward a new medical framework by using HDL-like nanoparticles to locate high-risk atherosclerotic plaques before they rupture and lead to heart attack or stroke.

Unlike researchers who are making particles that are either large and can cannot penetrate the wall of diseased vessels, or made from metals, semiconductors or other solid materials, this group is making lipid-based nanoparticles that are less than 10nm in diameter which are know to have ready access to the plaques in the vessel wall. More importantly, the reconstituted HDL (rHDL)-like nanoplatform, in which purified (and often truncated) Apolipoprotein A-1 (apo A-I), the primary protein component of HDL is used to form HDL nanoparticles with a variety of lipids, with and without cholesterol, can be made into homogeneous nanoparticles. rHDL can also be made out of shorther vesions of apo A-I. These engineered rHDL biological mimics interact with the vessel wall in very a specific way that allows them to accumulate at desired locations.

A variety of materials, such as a large quantity of gadolinium ions can be attached to the lipid layer of these nanoparticles which makes them easily visible on magnetic resonance imaging (MRI). The rHDL nanoplatform developed can be modified with small peptides or antibodies so that can be targeted to specific tissues, cells, and proteins.

In experimental preclinical work the group has shown that the rHDL MRI contrast agent behaved exactly as intended and is located specifically in the atherosclerotic vessel wall of living animals. They also showed that the rHDL nanoparticles were located in the inflamed (macrophage-rich) high-risk plaques.

Due to its mimicry of the natural biology, this rHDL nanoplatform is expected to be more practical, safer, and less costly than other more complex currently explored contrast agents. As several similar modified HDL forms are being developed for anti-atherosclerotic therapeutic purposes by Pfizer (apoa-1 milano), Novartis (D-4F), and others, this diagnostic HDL nanoplatform, will become quickly and widely accepted.

To date, a United States Utility patent has been filed. A PCT patent application has also been filed. The technology is available for licensing or sponsored research support. For further information, please contact Todd Pazdera, PhD. Tel: 212-659-9680 email: todd.pazdera@mssm.edu, Dr. Zahi A. Fayad. Tel: 212-241-6858 email: zahi.fayad@mssm.edu, or Dr. Edward A. Fisher. Tel: (212) 263-6331 email: edward.fisher@med.nyu.edu.