Doses of medicine 100,000 times smaller than the diameter of a human hair prevent the tissue damage associated with atherosclerosis and other chronic diseases in mice. As part of a National Institutes of Health-sponsored project led by Zahi Fayad, PhD, of the Icahn School of Medicine at Mount Sinai, researchers found that these nanomedicines are able to home specifically to damaged tissue to repair it. This study was published online this week in Proceedings of the National Academy of Sciences.
Inflammation is the body's natural defense mechanism against invading organisms and tissue injury. When under attack by a pathogen such as a virus, the body mounts an immune response that causes inflammation to clear the attacker so the body can return to a healthy state. Scientists believe that in chronic diseases like heart disease or diabetes, the body mounts a prolonged immune response resulting in chronic inflammation and tissue damage. Since the level of inflammation in these diseases is very high, targeted therapeutic solutions are required to help keep inflammation contained.
"Numerous studies have shown that inflammation is the foundation for many chronic diseases, and we need therapies that help resolve the tissue damage that results from that inflammation," said Dr. Fayad, who is the Director of the Translational and Molecular Imaging Institute and Professor of Radiology and Medicine at The Mount Sinai Medical Center. "Nanomedicine is the next frontier in successfully treating and preventing the progression of these conditions without the side effects that come from standard drug therapy."
Researchers at Brigham and Women's Hospital (BWH), Columbia University Medical Center, Massachusetts Institute of Technology, and Mount Sinai developed a nanoparticle that mimics a protein that is critical to the resolution of inflammation in the body. The research team incorporated the nanoparticle into a molecule consisting of three parts: one that controlled the release of the drug into the inflamed tissue, another that controlled how long it circulates in the system, and another that directs the drug to the damaged tissue in the vascular wall, where it binds to receptors in white blood cells.
"The beauty of this approach is that it takes advantage of nature's own design for preventing inflammation-induced damage, which, unlike many other anti-inflammatory strategies, does not compromise host defense and promotes tissue repair," said Ira Tabas, MD, PhD, physician-scientist at Columbia University Medical Center and co-senior author of this study.
The study showed that once the molecule was injected into mice, it homed to the injured tissue, where the drug was released into the vasculature as needed and circulated through the system, resolving the inflammation. These new developments have led the researchers to start investigating the potential of these pro-resolving nanomedicines for their effects on shrinking atherosclerotic plaques in humans.
"The development of self-assembled targeted nanoparticles which are capable of resolving inflammation has broad application in medicine including the treatment of atherosclerosis," said Omid Farokhzad, MD, physician-scientist at BWH, and a co-senior author of this study.
Mount Sinai received a contract for almost $16.5 million (#HHSN268201000045C) over five years from The National Institutes of Health (NIH) and the National Heart and Lung Institute (NHLBI) through the Program of Excellence in Nanotechnology (PEN). The contract is one of four issued nationally to develop multidisciplinary research centers with the goal of developing nanotechnology tools for diagnosing and treating heart, lung and blood diseases.
As co-principal investigator, Dr. Fayad leads a team of world-renowned experts in the fields of cardiology, imaging, and bioengineering. He is joined by the center's other co-principal investigator Robert S. Langer, ScD, Massachusetts Institute of Technology, for this highly collaborative program aimed at utilizing nanotechnology to better prevent and treat cardiovascular disease.