Scientists Create “Good Cholesterol” Particles To Treat Heart Disease
14 Mar 2016 --- US scientists have taken a first step towards treating heart disease and strokes by using microscopic particles that clear clogged arteries.
Researchers have created an artificial version of the ‘good’ cholesterol molecule, high density lipoprotein (HDL), that is known to protect against heart disease. The findings were presented at the 251st national meeting of the American Chemical Society in San Diego, California.
The molecule has a dual function - both ‘lighting up’ hard deposits on artery walls so they can be seen in scans, and helping to remove them.
Arterial wall deposits, called atherosclerotic plaques, are made from fatty material, cholesterol, calcium, and other substances.
Over time they cause blood vessels to narrow, restricting blood flow to heart muscle or the brain which can lead to heart attacks and strokes.
HDL takes ‘bad cholesterol’, or low-density lipoprotein (LDL), from the plaques and transports them to the liver, where they are eliminated from the body.
Lead scientist Dr Shanta Dhar, from the University of Georgia, said: "Other researchers have shown that if you isolate HDL components from donated blood, reconstitute them and inject them into animals, there seems to be a therapeutic effect. However, with donors' blood, there is the chance of immunological rejection. This technology also suffers scale-up challenges.”
"Our motivation was to avoid immunogenic factors by making a synthetic nanoparticle which can functionally mimic HDL. At the same time, we wanted a way to locate the synthetic particles."
The molecules contain iron oxide which acts as a ‘contrast agent’ that shows up in magnetic resonance imaging (MRI) scans. This allows them to ‘light up’ the atherosclerotic plaques they cling to so their location in the body can be pinpointed.
To simultaneously identify and treat atherosclerosis without triggering an immune response, Dhar and Bhabatosh Banik, Ph.D., a postdoctoral fellow in her lab, created an MRI-active HDL mimic. The researchers had previously built synthetic HDL particles lacking a contrast agent. These particles lowered levels of total cholesterol and triglycerides in mice.
"The key challenge, then, was designing the contrast agent," Banik says. "It took time to figure out the optimal lipophilicity and solubility."
The contrast agent, iron oxide, needed to be encapsulated in the synthetic lipoparticle's hydrophobic core to provide the brightest possible signal. Eventually, the researchers hit on the right chemical combination—iron oxide with a fatty surface coating—for optimal particle encapsulation. They successfully visualized the contrast agent using MRI in cell studies.
So far, the research has involved tests only on cells, but the scientists plan to move onto a clinical trial within two years.
