An injectable hydrogel for synergistic therapy in colorectal cancer by targeting glutathione

Summary

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, with chemoresistance driven by elevated intratumoral glutathione (GSH) levels posing a major challenge for effective treatment. Here we report a multi-enzyme-like hydrogel (MELH), composed of thiolated carboxymethyl cellulose (CMC-SH), designed to deplete GSH and enhance the efficacy of 5-fluorouracil (5-FU). MELH modulates the tumor microenvironment through multi-functional roles, including glucose depletion and reactive oxygen species (ROS) generation. In cell-derived and patient-derived xenograft models, MELH significantly reduces tumor growth, increases apoptosis, and exhibits synergistic anti-tumor effects without notable toxicity. These findings demonstrate that MELH is an effective adjuvant therapy to overcome chemoresistance and improve treatment outcomes for advanced CRC.