Scientists have developed targeted, biodegradable nano "drones" to deliver anti-inflammatory drugs that heal and stabilize arterial plaque in mice. Their work could pave the way for more effective prevention of heart attack and stroke in humans caused by atherosclerosis, in which artery walls thicken and suffer reduced plasticity due to an accumulation of white blood cells.
The study, conducted by researchers from Colombia University Medical Center (CUMC), Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS), showed for the first time that it is possible to treat inflammation and repair plaques via highly targeted nanoparticles. It is also the first example of using targeted nanomedicine to reduce atherosclerosis in animals.
Essentially, the nanoparticles are injected into the bloodstream where they find their way to the arterial plaque, stick to them and release the healing peptides. Their small size – they are 1,000 times smaller than the tip of a single strand of human hair – and "sticky" surfaces enable them to accumulate and be retained within the plaques to facilitate healing and remodeling to block plaque rupture and thrombosis.
"[The nanometer-sized drones] reach the plaque within hours and slowly release the drug," Dr Ira Tabas, co-senior author, MD, Richard J. Stock Professor of Medicine (Immunology) and professor of pathology & cell biology at CUMC told Gizmag. "Then it takes a few weeks for the drug to remodel the plaques so they are more stable."
Researchers at BWH developed the nanoparticles using biodegradable, FDA-approved polymers engineered to carry the healing, stabilizing anti-inflammatory peptides. The polymers are designed to break up over time in the body.
After five weeks of treatment, mice with advanced artherosclerosis demonstrated significant repair to damaged arteries as well as stabilization of plaque. The study represents a different approach to treating atherosclerosis, the leading cause of death in the United States.
“Many researchers are trying to develop drugs that prevent heart attacks by tamping down inflammation, but that approach has some downsides,” says Dr Tabas. “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. Using this approach to prevent a heart attack that may never happen may not be worth the risk.”
“Atherosclerosis is not only inflammation; there’s also damage to the arterial wall," adds Columbia associate research scientist Gabrielle Fredman, PhD, one of the study’s lead co-authors. "If the damage isn’t repaired, you may not prevent heart attacks.”
Trials on humans are still some years away, with further optimization and testing required. However, Dr Tabas expects that even better delivery to plaques can be obtained and improved healing possible than that provided with the current peptides.
The team envisions the drug would be given to people at the highest risk for heart disease, and that it would only work while the people are taking the nanoparticles. However, if at the same time, LDL-lowering therapy is also given and maintained indefinitely, then it's possible that the plaque-stabilizing nanomedicine could be discontinued after a few years.
The findings were published in the Feb. 18 online issue of Science Translational Medicine.
The technique is described in the video below.
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