Careening through the bloodstream, a single nanoparticle is dwarfed by red blood cells whizzing by that are 100 times larger. But when specially designed nanoparticles bump into an atherosclerotic plaque — a fatty clog narrowing a blood vessel — the tiny particles can play an outsized role. They can cling to the plaque and begin to break it down, clearing the path for those big blood cells to flow more easily and calming the angry inflammation in the vicinity.
By finding and busting apart plaques in the arteries, nanoparticles may offer a new, non-surgical way to reduce a patient’s risk for heart attack and stroke.
Nanoparticles measure less than 100 nanometers across — a thousandth the thickness of a dollar bill. Despite being tiny, they can be engineered to haul a mix of molecules — such as tags that make them stick to a plaque, drugs that block inflammation or dyes that let scientists track their movements. Over the last two decades, scientists have exploited these strategies to fight cancer, designing nanoparticles that deliver drugs (SN Online: 1/3/14) or dyes for imaging deep into the core of a tumor. The U.S. Food and Drug Administration has approved a few dozen cancer-focused nanomedicines.
Drugs, dyes and targeting molecules can be arranged on the perimeter or inside of a nanoparticle (illustration shows one that mimics HDL).
S. MARRACHE AND S. DHAR/PNAS 2013
Now researchers have begun engineering nanoparticles to target cardiovascular disease, which kills even more people each year than cancer. Nanosized compounds have been built that can sweep into clogged arteries to shrink the plaques that threaten to block blood flow. Some nanoparticles home in on the plaques by binding to immune cells in the area, some do so by mimicking natural cholesterol molecules and others search for collagen exposed in damaged vessel walls. Once at the location of a plaque, either the nanoparticles themselves or a piggybacked drug can do the cleanup work.
The aim of all these approaches is to prevent strokes and heart attacks in people with cardiovascular disease, either before surgery becomes necessary or after surgery to prevent a second event. Today, cardiovascular nanoparticles are still far from pharmacy shelves. Most have not reached safety testing in patients. But in mice, rats and pigs, nanodrugs have slowed the growth of the plaques that build up on vessel walls, and in some cases have been able to shrink or clear them.
“I think the effect we can have with these nanoparticles on cardiovascular disease is even more pronounced and direct than what we’ve seen in cancer,” says Prabhas Moghe, a biomedical engineer at Rutgers University in Piscataway, N.J.
Every minute, more than a gallon of blood pumps through the human heart, pushing through miles of blood vessels to deliver oxygen and nutrients to organs and extremities. In a healthy person, the trip is as smooth as a drive on a freshly paved highway. But in the more than 10 percent of U.S. adults who have cardiovascular disease, the route might be more like a pothole-filled road squeezed by Jersey barriers.
Waxy globs, or plaques, of fat and cholesterol line the blood vessels, thickening and hardening the walls, impeding blood flow. As fat builds up inside the vessels, it also leaks into the vessel walls, swelling them and signaling the body to send immune cells to the area. The congregation of immune cells aggravates the blockage, the way emergency vehicles surrounding the site of a multi-car pileup further slow traffic on a highway.
“The inflammation and the accumulation of fat in the walls of the blood vessel sort of feed off each other and exacerbate each other,” Moghe says.
If the plaques grow large enough, or pieces chip off and travel to smaller vessels, they can block a vessel. If oxygen-filled blood can’t reach the brain or heart, a stroke or heart attack results.
The drugs most often prescribed to prevent or treat atherosclerosis — plaque buildup on the inner walls of the arteries — are statins (SN: 5/5/12, p. 30). This highly successful and effective class of drugs, available since 1987, slows the growth of the fatty plaques by lowering the amount of cholesterol circulating in the blood. But taking statins is akin to limiting the number of cars on a damaged road rather than repairing potholes, some argue. And the drugs can boost a person’s risk of diabetes and liver damage. In many cases, patients don’t begin taking statins until they already have severe atherosclerosis, and the drugs do little to reverse the buildup of plaques that already exist.
“Heart disease is still the number one killer in the U.S.,” says endocrinologist and biochemist Ira Tabas of Columbia University Medical Center. Drug-carrying nanoparticles that can shrink existing atherosclerotic plaques and eliminate the accompanying inflammation could change that, Tabas and others say.