Hilderbrand, Scott, PhD
Research
Our research group is focused on the development of emerging fluorochrome and nanoparticle technologies for molecular imaging applications. To image effectively in vivo, dyes with absorption and fluorescence emission maxima in the NIR (650-950 nm) are necessary. Active research projects are centered on the synthesis of fluorochromes with enhanced optical characteristics for labeling, use in enzyme activated probes, and design of environment-responsive fluorogenic probes. Additional projects are focused on the construction of improved fluorescence and/or multimodal nanoparticle-based imaging platforms.
Currently, we are investigating synthesis of modified NIR dyes that are optimized for labeling nano-scaffolds such as cross-linked iron oxide (CLIO) particles, bacteriophage, and poly lactic-co-glyclolic acid (PLGA) nanoparticles. Nanoparticles based on these new dyes will offer improved signal for a multitude of targeted and fluorogenic imaging applications.
Another area of interest is the development NIR fluorochromes, which display altered optical properties upon changes in their local microenvironments. Projects include the design of dyes that respond to alterations of local ion concentrations, dielectric constant shifts, and oxidizing environments. One emerging application of these environment-responsive fluorochomes is in atherosclerosis imaging. Myleoperoxidase, an enzyme that is highly upregulated in vulnerable atherosclerotic plaques, produces hypochlorite, a strong oxidant under physiological conditions. A new naphthofluorescein based probe currently under development in our laboratory is activated selectively by hypochlorite. With this hypochlorite-responsive fluorochrome, we hope to ultimately image and identify vulnerable plaques.