A water-soluble 1,8-naphthalimide-based fluorescent pH probe for distinguishing tumorous tissues and inflammation in mice.

ABSTRACT

A water-soluble fluorescent probe BPN, by introducing a piperazine as the pH-sensitive fluorescence signaling motif to the hydrophilic propionic acid-substituted 1,8-naphthalimide fluorophore, is highly sensitive to pH changes within cytoplasm matrix in living cells, as well as pH-related diseases models. Owing to the protonation-induced inhibition of the photoinduced electron transfer (PET) from piperazine to naphthalimide fluorophore, BPN displayed a significant fluorescence enhancement (more than 131-fold) upon the pH decreasing from 11.0 to 3.0. The linear range was between pH 6.4 to 8.0 with a pKa value of 6.69 near the physiological pH, which was suitable for cytosolic pH research. Furthermore, BPN exhibited a large Stokes shift (142 nm), good water solubility, excellent photostability, high selectivity and low cytotoxicity. All these advantages were particularly beneficial for intracellular pH imaging. Using BPN, we demonstrated the real-time monitoring of cytosolic pH changes in living cells. Most importantly, BPN has not only been successfully applied for distinguishing inflammation in mice, but also the surgical specimens of cancer tissue, making it of great potential application in cancer diagnosis.