Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma

Yandong Wang, Haodong Li, Junyang Lin, Yutang Li, Keqin Zhang, Hui Li, Qiang Fu () and Yanyan Jiang ()
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Yandong Wang: Shandong University
Haodong Li: Shandong University
Junyang Lin: Shandong First Medical University
Yutang Li: Shandong University
Keqin Zhang: Shandong First Medical University
Hui Li: Shandong University
Qiang Fu: Shandong First Medical University
Yanyan Jiang: Shandong University

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: 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 ZnFe2O4@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 H2O2, thereby inducing multiple ROS bursts. Furthermore, these comprehensive effects up-regulate the HMOX1 to promote the Fe2+ 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.

Date: 2025
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DOI: 10.1038/s41467-025-57190-1

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