Developmental Project 2 - NIR NP probes to measure ROS and NO
Project Leader - Mikhail Y. Berezin, Ph.D.
The goal of this Developmental Project is to develop activatable near infrared fluorescent probes for measuring concentrations of reactive oxygen species (ROS) and nitric oxide (NO) in lungs after injury to monitor the effect of therapy.
Pulmonary responses to acute lung injury are mediated through enhanced production of ROS and NO by alveolar macrophages. A continuous measurement of the ROS and NO level in vivo is critical for a prompt selection of an appropriate therapy and monitoring its outcome. Fluorescence imaging using NIR contrast probes has recently become a sensitive method for studying pathological processes in vivo. While fluorescent sensors for ROS and NO based on small molecules have been developed, they have limited applicability to in vivo imaging, due to their fast clearance and instability. We propose to develop ROS and NO activatable fluorescent sensors by incorporating fluorophores into a NP platform. The sensors will be designed to be quenched in the absence of the targeted molecule (ROS or NO) and when activated, will fluoresce between 700 and 900 nm, in the range ideal for in vivo imaging, due to transparency of the tissue, thus providing a method for diagnosing lung pathologies and monitoring the effects of therapies.
Accordingly, the following Specific Aims are proposed:
- Synthesize and characterize activatable NIR fluorescent dyes for ROS and NO in a degradable NP protective environment.
- Test NIR fluorescent NPs in vitro and for in vivo imaging.