(5bn) Engineering Nanomaterials for Bioimaging and Therapeutic Applications

Hydrogen peroxide is an essential oxygen metabolite in living organisms, and is emerging as a newly recognized messenger in cellular signal pathways. However, the overproduction of hydrogen peroxide leads to oxidative stress and functional decline of organ systems, and has been observed in several life-threatening diseases such as atherosclerosis, cancer, and Alzheimer's and related diseases. Despite the significance of hydrogen peroxide in human health, at present, there are no contrast agents that can image hydrogen peroxide in vivo with sensitivity and selectivity. Therefore, there is great need in developing contrast agents that can image hydrogen peroxide in vivo.

I have developed peroxalate nanoparticles which detect hydrogen peroxide based on peroxalate chemiluminescence. Peroxalate nanoparticles were composed of peroxalate ester containing polymers and fluorescent dyes, and were designed to image hydrogen peroxide by performing a three component chemiluminescence reaction; first, hydrogen peroxide diffuses into the nanoprobes and reacts with peroxalate esters to generate a high energy intermediate dioxetane, second, dioxetane chemically excites fluorescent dyes, leading to light emission and imaging of hydrogen peroxide. Peroxalate nanoparticles with a mean size of 550 nm were capable of detecting hydrogen peroxalate with high sensitivity and specificity and were also capable of imaging hydrogen peroxide in the peritoneal cavity of mice, after a direct intraperitoneal injection. I have also developed peroxalate micelles in order to enhance physicochemical properties needed for intravenous applications. Peroxalate micelles had peroxalate esters and fluorescent dyes in their hydrophobic core and a stealth PEG corona. Peroxalate micelles had a mean diameter of 33 nm and were capable of detecting hydrogen peroxide at concentrations as low as 50 nM. It is anticipated that peroxalate-based nanoprobes have great potential for imaging of hydrogen peroxide in vivo, given their physicochemical properties and nanomolar sensitivity.