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Targeted Nanoparticles for Mitochondrial Medicine
Abstract: Mitochondrial dysfunctions cause many human disorders. In the recent years, targeting mitochondria emerged as an attractive strategy to control mitochondrial dysfunction related diseases. Despite the desire to direct therapeutics to the mitochondria, the actual task is more difficult due to the highly complex nature of the mitochondria. A platform technology for carrying bioactive molecules to different mitochondrial compartments could be of enormous potential benefit in medicine. Only a handful of nanoparticles (NPs) based on metal oxides, gold nanoparticles, dendrons, carbon nanotubes, and liposomes were recently engineered to target mitochondria. Most of these materials face tremendous challenges when administered in vivo due to their limited biocompatibility. We are developing hybrid biodegradable NP systems for their potential use in organelle targeting, combination therapy of cancer, combined neuroprotectatnt-stem cell therapy of neurodegenerative diseases, and image-guided therapy of atherothrombotic vascular diseases. We are developing rationally designed, programmable NP platform for diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction related diseases. An optimized formulation for maximal mitochondrial uptake was identified through in vitro screening of a library of charge and size varied NPs and the uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with mitochondria-targeted blended NPs. The versatility of this platform was demonstrated by studying a variety of mitochondria-acting therapeutics for different applications. These include mitochondria targeting chemotherapeutics for cancer, mitochondrial antioxidant for diseases of central nervous system, and mitochondrial uncoupler for obesity. On the cardiovascular front, we are developing a long-circulating hybrid NPs that can mimic the properties of high-density lipoprotein in the management of vascular diseases.
Biography: Dr. Shanta Dhar was born in West Bengal, India. She received her Ph. D. from the Indian Institute of Science, Bangalore, India. Her graduate work was in the area of bioinorganic chemistry with the overall goal to develop copper(II) complexes to effect photocleavage of double stranded DNA at longer wavelengths. She was awarded with Prof. S. Sunderajan Best thesis award, Indian Institute of Science (2005). In 2006, she came to this side of the globe and joined Johns Hopkins University as a postdoctoral fellow where she worked in the area of bioorganic chemistry with Prof. Marc M. Greenberg. During 2007-2010, Dr. Dhar was an Anna Fuller postdoctoral fellow in Prof. Stephen J. Lippard’s group at the Massachusetts Institute of Technology and her postdoctoral studies were focused on nanocarrier-mediated delivery of platinum-based drugs for their potential applications in cancer. Dr. Dhar joined the chemistry department at the University of Georgia as an assistant professor in August 2010. Dr. Dhar’s research interests focus on nanomedicine with particular interests in mitochondrial-dysfunction related diseases. She has published over 45 peer-reviewed articles and holds 10 patents on these topics. She has received Ralph E Powe junior faculty award (2011), Department of Defense Prostate Cancer Idea Development award (2012), Targeting Mitochondria 2012 Award for Scientific Contribution, American Heart Association Scientist Development award 2013, Georgia’s Top biomedical researcher 2014, Georgia’s 40 under 40, 2014, Thieme Chemistry Journal Award 2015, co-founder of PartiKula LLC.
Faculty Host: Linda Doerrer