Two independent research teams have used nanotechnology approaches to directly treat atherosclerotic plaques, by preventing their formation and stabilizing them, respectively.

Atherosclerosis, the narrowing of arteries due to plaque buildup, can lead to heart attacks and strokes, but also peripheral artery disease and kidney disease.

The worst of those problems come when a plaque ruptures, breaking off from the cell wall and entering the bloodstream. Ruptured plaques can block an artery, leading to a stroke.

But even plaques that stay put can cause problems, because they impede blood flow at the site where they are located. "When they fester, they lead to a localized problem, which can then become a whole-body problem," Rutgers University's Prabhas Moghe told BioWorld Today.

The impeded blood flow can lead to pain, and tissue damage. If they are located in the legs, clots can lead to difficulty walking, and in the worst cases make it necessary to amputate the affected leg.

Current approaches to plaques "look at the problem in a very systemic way," Moghe said. Prevention, in the form of statins, is focused on lowering the levels of LDL cholesterol in the bloodstream.

But the bloodstream itself is not where LDL cholesterol is a problem. The problem starts when LDL cholesterol accumulates on vessel walls, and continues when the immune system cells try to respond to those LDL accumulations. Those macrophages then get stuck in the plaques, exacerbating the problem they were meant to fight.

Moghe is the corresponding author of one of two papers that appeared last week describing nanotechnology approaches that target the plaques directly.

In their experiments, which were published in the Feb. 16, 2015, online issue of the Proceedings of the National Academy of Sciences, Moghe and his team designed sugar-based nanoparticles that homed to plaques and prevented macrophages from taking up oxidized LDL cholesterol. Mice treated with the nanoparticles had reduced arterial thickening and plaque formation.

A second paper, in the Feb. 19, 2015, issue of Science Translational Medicine, used nanoparticles to deliver a peptide that helped resolve inflammation. The biological milieu inside of plaques is characterized by chronic inflammation, which drives several processes that can lead to plaque rupture, including a thinning of the collagen matrix that holds the plaque in place and necrosis within the plaque itself. By resolving that inflammation, the authors were able to reduce both thinning and necrosis, which had the net effect of stabilizing the plaques.

Comparing the two papers, Moghe said that "what they have is a biological approach . . . ours is a synthetic approach that is inspired by the biology."

The papers are also "looking at two different entry points into the disease," though both target the plaques directly rather than points upstream.

Moghe said his team is "extremely interested" in translating their findings, which were funded partly by a Wallace H. Coulter Foundation grant.

Being supported by the Coulter Foundation, Moghe said, was helpful because "they have a whole ecosystem" aimed at helping academic researchers to bring new technologies to patient care. The nanoparticles are in the process of being licensed to a nascent startup, Lipotherics Inc., which will continue with the preclinical studies necessary before taking the approach into patients.

As for the paper published in Science Translational Medicine, one of its co-authors is Omid Farokhzad, who is a co-founder of three nanobiotechnology companies: Bind Biosciences Inc., Selecta Biosciences Inc. and Blend Therapeutics Inc. For now, however, the work is being carried out in Farokhzad's lab at Harvard Medical School, and by academic colleagues at Columbia University and elsewhere. "Bind, Selecta, and Blend did not support the research in this study, and currently these companies have no rights to any technology or intellectual property developed as part of this research," the authors noted.