Nanoparticle Eat Atherosclerotic Plaques to Prevent Heart Attack
Atherosclerosis is a disease in which plaque builds up inside the arteries.
Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows the arteries. This limits the flow of oxygen-rich blood to the organs and other parts of the body.
Atherosclerosis can lead to serious problems, including heart attack and stroke.
It’s the world’s No. 1 killer. Available therapies treat risk factors such as high blood pressure and high cholesterol but fail to address the accumulation of diseased cells and inflammation within artery walls.
Atherosclerosis can affect any artery in the body, including arteries in the heart, brain, arms, legs, pelvis, and kidneys. As a result, different diseases may develop based on which arteries are affected.
Figure A shows a normal artery with normal blood flow. The inset image shows a cross-section of a normal artery. Figure B shows an artery with plaque buildup. The inset image shows a cross-section of an artery with plaque buildup. [nhlbi.nih.gov ©]
Atherosclerosis-Related Diseases
Ischemic Heart Disease
Ischemic heart disease happens when the arteries of the heart cannot deliver enough oxygen-rich blood to the tissues of the heart when it is needed during periods of stress or physical effort.
Coronary heart disease, also called coronary artery disease, is a type of ischemic heart disease caused by the buildup of plaque in the coronary arteries that supply oxygen-rich blood to the heart.
This buildup can partially or totally block blood flow in the large arteries of the heart. If blood flow to the heart muscle is reduced or blocked, you may have angina (chest pain or discomfort) or a heart attack.
Coronary microvascular disease is another type of ischemic heart disease. It occurs when the heart’s tiny arteries do not function normally.
Carotid Artery Disease
Carotid (ka-ROT-id) artery disease occurs if plaque builds up in the arteries on each side of the neck (the carotid arteries). These arteries supply oxygen-rich blood to the brain. If blood flow to the brain is reduced or blocked, you may have a stroke.
Peripheral Artery Disease
Peripheral artery disease (P.A.D.) occurs if plaque builds up in the major arteries that supply oxygen-rich blood to the legs, arms, and pelvis.
If blood flow to these parts of the body is reduced or blocked, you may have numbness, pain, and, sometimes, dangerous infections.
Chronic Kidney Disease
Chronic kidney disease can occur if plaque builds up in the renal arteries. These arteries supply oxygen-rich blood to the kidneys.
Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body.
Nanoparticle Therapy
Michigan State University and Stanford University scientists have invented a nanoparticle that eats away from the inside out portions of plaques that cause heart attacks.
Bryan Smith, associate professor of biomedical engineering at MSU, and a team of scientists created a nanoparticle that can be directed to eat debris, reducing and stabilizing plaque.
The results, published in the current issue of Nature Nanotechnology.
“This is precision medicine,” said Nicholas Leeper, MD, professor of vascular surgery and cardiovascular medicine. “We used the nanotubes to deliver a payload like a Trojan horse.”
Diseased and dying cells in artery plaque give off a “don’t eat me” signal, preventing the immune system’s waste-removal cells, known as macrophages, from engulfing them. The same signal is found on the surface of many types of cancer cells, allowing them to escape detection and multiply. The Leeper lab had previously reported in Nature that certain antibody-based therapies could block this cloaking signal and prevent plaque growth in mice. Unfortunately, this non-targeted approach also resulted in macrophages removing some healthy cells, thus limiting its chance of becoming a new treatment for heart disease.
Smith developed a nanotube to carry a molecule that turns off the “don’t eat me” signal. Unlike the nonspecific antibodies, these nanotubes were taken up by white blood cells (thus the Trojan horse metaphor) that made their way to inflammatory sites such as artery plaque. Once they were inside the plaque, these white blood cells — known at that point as macrophages — “ate up” diseased and dying cells.
“We reactivated their ability to recognize them as a disease, gobble them up and take out the trash,” Leeper said. “But best of all, we didn’t see any significant toxicities this time.”
The researchers found that the nanotherapy reduced plaque by 40% in both female and male mice with less advanced plaque, and it reduced the plaque by 20% in male mice with more advanced plaque.
Because the white blood cells that took in the nanotubes went to artery plaque rather than to healthy tissue, Smith said, the nanotherapy avoided side effects such as anemia and organ damage.
“We were able to constrain the uptake into just the cells we want,” he said. “There’s a general rule of treatment: The more targeted you can get, the fewer side effects you have.”
Smith said that future clinical trials on the nanoparticle are expected to reduce the risk of most types of heart attacks, with minimal side effects due to the unprecedented selectivity of the nanodrug.
Other applications
Flores said their finding has additional treatment implications. “It’s an exciting development, not only for cardiovascular disease, but also for cancer,” she said.
“One might ask: Can it treat cancer?” he said. “We think so. However, such other diseases require more speculation. This strategy improves on existing treatments because of its selectivity. The nanoparticle is exquisitely selective toward inflammatory monocytes and macrophages, which allows it to decrease side effects that may be associated with other treatments.”
The work has yet to progress to human trials. So far, the researchers have proven efficacy in a culture dish and in two types of mice that have developed atherosclerosis. They next plan to test large animal models and human tissues, as well as look at how their nanotherapy measures up to other available treatments. They’re also exploring how the nanoparticles could potentially be used as diagnostic imaging tools, highlighting particular cells.