Diketopyrrolopyrrole-based multifunctional ratiometric fluorescent probe and -glutamyltranspeptidase-triggered activatable photosensitizer for tumor therapy

Photosensitizers can generate highly reactive oxygen species (ROS) by light excitation, causing cell damage and apoptosis. However, conventional photosensitizers cannot kill cancer cells selectively. In this work, we report a series of diketopyrrolopyrrole (DPP)-based photosensitizers, in whichDPP-pywith one pyridine group exhibits superior photodynamic killing effect on tumor cells. Furthermore, by introducing 4-bromomethyl-phenyl glutamic acid inDPP-py, we adopt a strategy involving the intramolecular charge transfer effect to develop a multifunctional DPP-based ratiometric fluorescent probe and activatable photosensitizerDPP-GGT, which can target the tumor-related biomarker gamma-glutamyltranspeptidase (gamma-GT).DPP-GGTshows highly selective and obvious fluorescent changes from red to yellow for gamma-GT. More importantly,DPP-GGTexhibits specific photodynamic killing effects on human hepatic cancer cells HepG2 due to the high activity of endogenous gamma-GT but no marked phototoxicity toward low-gamma-GT-expressing breast cancer cells MCF-7 or normal hepatocyte cells L02. The results demonstrate thatDPP-GGThas great potential for the tumor-specific activatable photodynamic anticancer therapy.