Abstract
Conventional immunotherapy exhibits low response rates due to the immunosuppressive tumor microenvironment (TME). To overcome this limitation, this study introduces ZFPG nanoparticles (ZFPG NPs) with ZnFe(2)O(4)@Pt cores and glucose oxidase (GOx) shells. The ZFPG NPs possess five-enzyme activities, good sonosensitivity, and remarkable magnetic targeting properties, which facilitate sono-metallo-immunotherapy for prostate cancer treatment in male mice. Specifically, the magnetic targeting ability effectively improves their accumulation in tumors while still showing enrichment in the liver and kidneys. The multienzyme cascade catalysis and sonosensitivity of these NPs effectively deplete glutathione and glucose, and enhance the generation and utilization of H(2)O(2), thereby inducing multiple ROS bursts. Furthermore, these comprehensive effects up-regulate the HMOX1 to promote the Fe(2+) and lipid peroxides accumulation, thereby inducing immunogenic ferroptosis. This strategy facilitates anti-tumor immunity by ameliorating the immunosuppressive TME and inhibiting lung metastatic progression. This joint warfare strategy offers a powerful solution to address conventional immunotherapy limitations.