A Metabolic Multistage Glutathione Depletion Used for Tumor-Specific Chemodynamic Therapy

The high glutathione (GSH) content in tumor cells strongly affects the efficiency of chemodynamic therapy (CDT). Despite devoted efforts, it still remains a formidable challenge for manufacturing a tumor-specific CDT with rapid and thorough depletion of GSH. Herein, a multistage GSH-consuming and tumor-specific CDT is presented. By consuming the reserved GSH and inhibiting both the raw materials and energy supply of GSH synthesis in cancer cells, it achieves highly potent GSH exhaustion. Our used glycolysis inhibitor cuts off the specific glycolysis of tumor cells to increase the sensitivity to CDT. Furthermore, the starvation effect of glycolysis inhibitor can stimulate the protective mode of normal cells. Since the glycolysis inhibitor and nanocarrier are responsive to tumor microenvironment, this makes CDT more selective to tumor cells. Our work not only fabricates nanomedicine with GSH exhausted function for highly potent CDT but also uses metabolic differences to achieve tumor-specific therapy.

Automated summary

In this study, a multistage chemodynamic therapy (CDT) specific to tumor cells is proposed, which can efficiently deplete the high glutathione (GSH) content in tumor cells. By consuming reserved GSH and inhibiting GSH synthesis in cancer cells, the CDT achieves potent GSH exhaustion. The glycolysis inhibitor used in this study not only increases the sensitivity of tumor cells to CDT, but also stimulates a protective mode in normal cells. This tumor-specific CDT utilizes the responsiveness of the glycolysis inhibitor and nanocarrier to the tumor microenvironment.