February 16, 2011
FRONTIERS IN MATERIALS SCIENCEDr. Niren Murthy
VINSE COLLOQUIUM SERIES
Wallace H. Coulter Dept. of Biomedical Engineering
Georgia Institute of Technology
"New materials for drug delivery and molecular imaging"
Abstract. Drug delivery and molecular imaging have tremendous potential for improving human healthcare, however their medical impact has been limited because of a lack of materials. In this presentation I will describe four new materials that are designed to improve the delivery of therapeutics and image disease biomarkers. Two materials for drug delivery will be described, polythioketal nanoparticles (TKNs) and hoechst-gemcitabine (H-gemcitabine). TKNs are nanoparticles formulated from polythioketals, and are designed to target orally delivered therapeutics to intestinal inflammation. TKNs are stable to acid and base, but degrade in the presence of reactive oxygen species (ROS), allowing them to target intestinal inflammation, which has upregulated ROS levels. We demonstrate that orally administered TKNs can deliver TNFα-siRNA, diminish TNFα mRNA in the colon and protect mice from intestinal inflammation. H-gemcitabine is an auto-catalytic drug delivery vehicle designed to treat cancer, it is composed of the DNA binding agent Hoechst conjugated to gemcitabine. H-gemcitabine targets tumors by binding extracellular DNA (E-DNA) and also increases the tumor E-DNA concentration, by killing tumor cells. We demonstrate that H-gemcitabine has autocatalytic drug targeting properties, and is significantly more effective at treating xenografted tumors in mice than free gemcitabine. Two materials for molecular imaging will also be described, the hydrocyanines and metabolic imaging probes (MIPs). The hydrocyanines are a family of fluorescent ROS probes that can detect superoxide and the hydroxide radical in vivo. We are currently collaborating with numerous laboratories on using hydrocyanines, and anticipate that the hydrocyanines will have a significant impact on ROS biology, given their unique ability to measure radical oxidants in vivo. Finally, I will present a new contrast agent for imaging bacteria, termed MIPs, which are designed to target the maltodextrin transport pathway and diagnose bacterial infections at an early stage.