NIR photosensitizers activated by γ-glutamyl transpeptidase for precise tumor fluorescence imaging and photodynamic therapy

Photodynamic therapy (PDT), a light triggered therapeutic mode, has been recognized as an attractive treatment for oncotherapy. The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always “on” properties of photosensitizers. Activatable photosensitizers are of great importance for improving the selectivity of PDT. Herein, we regarded the overexpressed GGT (γ-Glutamyl transpeptidase) enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT, L-glutamic acid, to a hemicyanine dye based on photosensitizer Cy-NH2. Cy-GGT was in the “off” state with negligible fluorescence and suppressed singlet oxygen generation, but it could be specifically hydrolyzed to Cy-NH2 in the presence of GGT, accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation. The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.