Biochemical processes frequently involve protonation and deprotonation, resulting in pH changes that can be monitored with pH indicators. In heterogenous media such as tissue where indicator concentration or visual observation is limited, highly sensitive pH indicators with reduced tissue autofluorescence are needed. Because of the reduced tissue autofluorescence in the near infrared (NIR) region, NIR fluorescence dyes such as indocyanine green (ICG) and its
derivatives have been used to image molecular processes. Removing one of the N-subsitituent of ICG led to pHsensitive dyes operating in the NIR region and at physiologically relevant range. Further modification of the compound and synthetic procedure allowed their conjugation to peptides for specific delivery to target cells and tissues. Synthetic strategy and preliminary results on the spectral and biological properties of such dyes and their bioconjugates are described.
A new carbocyanine optical molecular probe with enhanced water solubility and constrained structural conformations was designed and synthesized. The near infrared (NIR) fluorescent probe contains a nonionic D-galactopyranose, which could improve water solubility of the probe and enhance uptake in tumors mediated by glucose transporter. The possibility of multiple attachment points provides the potential to conjugate diverse bioactive molecules to the probe. We developed an efficient synthetic method that is optimized for large-scale synthesis. Preliminary in vivo biodistribution studies show that the probe is rapidly cleared from blood and localize in the liver as early as 5 minutes post-injection of the probe in nude mice. Additional studies to evaluate the tumor uptake of the probe and its bioactive peptide conjugates are in progress.