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2007 Grant - Liu
Developing Nanoparticulated Iron Chelators to Deplete Brain Excess Metals
Gang Liu, Ph.D.
University of Utah
Salt Lake City, Utah
2007 Investigator Initiated Research Grant
Studies show that there is an excess of iron in the brains of patients with Alzheimer's disease. Removing this excess metal may be a viable therapeutic strategy. However, chelators, or chemicals that form tight complexes with transition metals such as iron, are often toxic or do not readily pass from the blood to the brain. Furthermore, once a chelator binds to a metal it can get trapped inside the brain, because the metal-chelator complex may pass very slowly back to the blood.
Gang Liu, Ph.D., and colleagues plan to develop tiny carriers, or nanoparticles, to circumvent some of the problems associated with traditional chelators. By coupling chelators to these nanoparticles, the researchers hope to improve their ability to pass in an out of the brain, even when bound to metals. This will improve their ability to clear the brain of iron and other toxic heavy metals.
The researchers plan to first synthesize new chelators, which can be chemically bound to inert nanoparticles. These will be tested for their ability to bind metals and also to pass into and out of the brain. They will then be tested in mouse models of Alzheimer's disease. The researchers will test how the nanoparticles clear iron from the brains of mice engineered to produce the human protein that makes amyloid plaques. These nanoparticles may not only prove useful as therapeutics, but may also be invaluable as imaging agents to monitor metal content in the brain.