Abstract
Hydrogen therapy has shown new potential in cancer treatment, particularly in high-pressure and hypoxic areas, where it demonstrates the ability to alter the tumor microenvironment and regulate tumor metabolism. Hydrogen disrupts the mitochondrial function of cancer cells, interferes with their energy metabolism, and ultimately leads to energy depletion and apoptosis. In this study, a sonocatalyst (BPM), is designed to generate hydrogen and oxygen in situ within tumors, further enhancing the therapeutic efficacy. The mesocrystalline structure of BPM, composed of bismuth fluoride, polyoxometalates, and molybdenum carbide, significantly improves charge separation and electron transfer efficiency under ultrasound irradiation, resulting in an efficient water-splitting reaction. By simultaneously generating hydrogen and oxygen within the tumor microenvironment and depleting glutathione, BPM effectively triggers oxidative stress and alleviates hypoxia, thereby disrupting mitochondrial function and inhibiting energy metabolism in cancer cells. Additionally, BPM enhances antitumor immune responses by promoting dendritic cell maturation, activating T lymphocytes, and polarizing macrophages toward the M1 phenotype, reversing the immunosuppressive state of the tumor microenvironment. The results indicate that BPM holds potential for gas-immunotherapy combination treatments, offering a multifunctional strategy to improve cancer therapy outcomes.