Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma
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 activit...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57190-1 |
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| author | Yandong Wang Haodong Li Junyang Lin Yutang Li Keqin Zhang Hui Li Qiang Fu Yanyan Jiang |
| author_facet | Yandong Wang Haodong Li Junyang Lin Yutang Li Keqin Zhang Hui Li Qiang Fu Yanyan Jiang |
| author_sort | Yandong Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1ef64be8f12c4200a4b2c3dbb72c767c |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1ef64be8f12c4200a4b2c3dbb72c767c2025-08-20T03:11:07ZengNature PortfolioNature Communications2041-17232025-02-0116112310.1038/s41467-025-57190-1Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinomaYandong Wang0Haodong Li1Junyang Lin2Yutang Li3Keqin Zhang4Hui Li5Qiang Fu6Yanyan Jiang7Key Laboratory for Liquid–Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong UniversityDepartment of Urology, Shandong Provincial Hospital, Shandong UniversityDepartment of Urology, Shandong Provincial Hospital, Shandong First Medical UniversityKey Laboratory for Liquid–Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong UniversityDepartment of Urology, Shandong Provincial Hospital, Shandong First Medical UniversityKey Laboratory for Liquid–Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong UniversityDepartment of Urology, Shandong Provincial Hospital, Shandong First Medical UniversityKey Laboratory for Liquid–Solid Structural Evolution & Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong UniversityAbstract 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.https://doi.org/10.1038/s41467-025-57190-1 |
| spellingShingle | Yandong Wang Haodong Li Junyang Lin Yutang Li Keqin Zhang Hui Li Qiang Fu Yanyan Jiang Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma Nature Communications |
| title | Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma |
| title_full | Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma |
| title_fullStr | Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma |
| title_full_unstemmed | Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma |
| title_short | Engineering nanozyme immunomodulator with magnetic targeting effect for cascade-enzyodynamic and ultrasound-reinforced metallo-immunotherapy in prostate carcinoma |
| title_sort | engineering nanozyme immunomodulator with magnetic targeting effect for cascade enzyodynamic and ultrasound reinforced metallo immunotherapy in prostate carcinoma |
| url | https://doi.org/10.1038/s41467-025-57190-1 |
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