Doxorubicin prodrug for γ-glutamyl transpeptidase imaging and on-demand cancer therapy.

The γ-glutamyl transpeptidase (γ-GGT) is an important tumor marker, which has been reported to be firmly associated with the developmental stage of liver cancer. Therefore, it makes sense to image and monitor γ-GGT level and design γ-GGT-responsive prodrug for integrated diagnosis and treatment of liver cancer. Herein, we prepare a doxorubicin (Dox) prodrug for imaging γ-GGT and on-demand treating liver cancer. When γ-GGT exists, the γ-glutamyl group will be cut off to liberate free Dox for monitoring cancer progression and killing tumor cells. Fortunately, little Dox is released due to the low level of γ-GGT in normal cells, which improves the safety and efficiency of chemotherapy. To further improve the tumor targeted ability, Dox prodrug is loaded in hyaluronic acid modified liposome nanoparticles to form the nano-prodrug. Then nano-prodrug is enriched in the tumor by binding to the high expressed CD44 on cancer cells. With the assistance of anti-PD-L1, nano-prodrug effectively inhibits the growth of proximal and distal tumors.