Engineering of Nanoparticles for Mitochondrial Trafficking of Therapeutics and Diagnosis of Cardiovascular Diseases

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Title: Engineering of Nanoparticles for Mitochondrial Trafficking of Therapeutics and Diagnosis of Cardiovascular Diseases
Author: Dhar, Shanta
Abstract: The potential benefits of integrating nanomaterials with properties such as biodegradability, magnetization, fluorescence, and near-infrared absorption into a single object of nanoscale dimensions can lead to the development of hybrid nano-medical platforms for simultaneous targeting, imaging, and combination therapy administration. We are developing hybrid nanoparticle (NP) systems such as hybrids of polymeric–gold nanoparticle and polymeric–iron oxide hybrid nanoparticle for their potential use in combination therapy of cancer and image-guided therapy of atherothrombotic vascular disease (ATVD), respectively. Mitochondrial dysfunctions cause many human disorders. A platform technology of carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in therapeutics. We are developing a rationally designed mitochondria-targeted NP system and its optimization for efficient delivery of a variety of mitochondria-acting therapeutics by blending a targeted poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-triphenylphosphonium (PLGA-b-PEG-TPP) polymer with either non-targeted PLGA-b-PEG-OH or PLGA-COOH. On the cardiovascular front, we are developing a long-circulating hybrid NP platform to selectively target macrophages and sense apoptosis for detection of plaque vulnerable to embolism. Apoptosis of cells along the arterial wall serves as a target for detection of plaque vulnerable to embolism. In this context, to detect atherosclerotic plaques noninvasively, we are developing MRI active NPs which can selectively target macrophages in the arteries and detect apoptotic cells with altered or compromised membranes. These highly engineered NPs include iron oxide in the core of a polymeric matrix for MRI detection, mannose for macrophage targeting, apoptotic cell targeting peptides, and a metal binding site for effective detection. The utility of these NPs in the diagnosis of atherosclerosis will be discussed.
Description: Shanta Dhar presented a lecture at the Nano@Tech Meeting on April 10, 2012 at 12 noon in room 1116 of the Marcus Nanotechnology Building. Dr. Dhar received her Ph.D. from the Indian Institute of Science, India. She was a postdoc in JHU where she developed sensors for detection of DNA lesions. In 2007, she joined MIT as an Anna Fuller fellow and worked on platinum-based cancer therapy. Currently, Dr. Dhar is an assistant professor in the chemistry department at the University of Georgia and an adjunct assistant professor in the Department of Physiology and Pharmacology. Her research program is in the field of nanomedicine. Dr. Dhar was recently awarded with Ralph E. Powe Junior Faculty Enhancement Award and Department of Defense Idea award. Runtime: 39:29 minutes
Type: Lecture
Date: 2012-04-10
Contributor: University of Georgia. Dept. of Chemistry
Publisher: Georgia Institute of Technology
Subject: Biomedical

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