This research plan represents the first combination of photoacoustic imaging with polymeric nanosensor technology. This approach couples the imaging depth and resolution of photoacoustics with the tunable sensor response and modular sensor design of nanosensors, enabling continuous monitoring of lithium concentrations in vivo. Bipolar disorder affects approximately 2.6% of the population and lithium is one of the most commonly used management treatments as it drastically reduces suicide risk. Unfortunately, lithium has a narrow therapeutic window and a low toxic dose. The proposed research is to develop lithium selective nanosensors which can be used for continuous monitoring of lithium concentrations in vivo as well as coupling these nanosensors with both fluorescent and photoacoustic imaging. This research will enable improved study of individualized pharmacokinetics and personalized medicine. Additionally, this research will set the groundwork for a wide range of future investigations utilizing the combination of photoacoustics and nanosensors. These include: monitoring metabolic profiles in tumors which are too deep to measure with fluorescence or drug concentration profiling in the brain and other organs.
The specific aims of this research are: 1) Develop and characterize absorbance and fluorescence based nanosensors for lithium detection and characterize in vitro 2) Demonstrate in vivo application of nanosensors using fluorescence imaging for monitoring subcutaneous lithium concentrations 3) Couple lithium nanosensors with photoacoustic microscopy to monitor blood lithium concentrations. This research couples together the Clark laboratory's experience with nanosensor development and testing with the photoacoustic microscopy experience of Lihong Wang's laboratory. The proposed research and training plan enable improve study of individualized pharmacokinetics and personalized medicine will provide ample training in both research techniques as well as career development which will leave me well placed for a future as an independent investigator in biomedical research.
This research plan represents the first combination of photoacoustic imaging with polymeric nanosensor technology. This combination will be used to monitor lithium concentration continuously in vivo to enable improve study of individualized pharmacokinetics and personalized medicine.
|Cash, Kevin J; Li, Chiye; Xia, Jun et al. (2015) Optical drug monitoring: photoacoustic imaging of nanosensors to monitor therapeutic lithium in vivo. ACS Nano 9:1692-8|
|Cash, Kevin J; Clark, Heather A (2013) Phosphorescent nanosensors for in vivo tracking of histamine levels. Anal Chem 85:6312-8|