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NEW YORK, NY (February 18, 2015) - Nanometer-sized "drones" that deliver a special type of healing molecule to fat deposits in arteries could become a new way to prevent heart attacks caused by atherosclerosis, if a recent study in mice by scientists at Columbia and Harvard universities is a guide. Full findings appear in the February 18 online issue of Science Translational Medicine.

In the study, biodegradable nanoparticles--loaded with a molecule that promotes healing --were injected into mice with advanced atherosclerosis. The nanoparticles were designed to home in on the hot spots of atherosclerosis in the arteries.

About 70 percent of the nanoparticles implanted themselves into atherosclerotic plaques and slowly released the drug. In these mice, the damage to the arteries was repaired, leading to a plaque that, in humans, would be less likely to cause heart attacks.

Atherosclerosis is driven by inflammation that is uncoupled from the body's normal repair response. In essence, the fat-containing particles (called low-density lipoproteins, or LDL) that stick to our arteries act like splinters in our skin. But whereas skin is repaired once splinters are removed, LDL deposits can last indefinitely and healing never starts.

These inflamed and damaged hot spots are the reason why atherosclerosis causes heart attacks. The spots are prone to rupture, and when they do, blood clots form around the break and obstruct blood flow to the heart.

Many researchers are trying to develop drugs that prevent heart attacks by tamping down inflammation, but that approach has some downsides, says Columbia atherosclerosis researcher Ira Tabas, MD, Richard J. Stock Professor of Medicine (Immunology) and professor of pathology & cell biology, one of the study's two senior leaders.

"One is that atherosclerosis is a chronic disease, so drugs are taken for years, even decades. An anti-inflammatory drug that is distributed throughout the entire body will also impair the immune system's ability to fight infection," he says. That might be acceptable for conditions that severely affect quality of life, like rheumatoid arthritis, but "using this approach to prevent a heart attack that may never happen may not be worth the risk." [Tabas & Glass, Science 2013]

In addition, it's not enough to deliver an anti-inflammatory drug to the plaques, says Columbia associate research scientist Gabrielle Fredman, PhD, one of the study's lead co-authors. "Atherosclerosis is not only inflammation; there's also damage to the arterial wall," she says. "If the damage isn't repaired, you may not prevent heart attacks."

Nature's way of starting repairs is with a suite of "resolving" molecules that extinguish inflammation and then initiate healing. Instead of packing the nanoparticles with anti-inflammatory drugs, Dr. Tabas's and Dr. Farokzhad's team packed them with pieces of a resolving protein called annexin A1.

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Precision nano 'drones' deliver healing drug to subdue atherosclerosis