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Transformable Tumor Microenvironment‐Responsive Oxygen Vacancy‐Rich MnO2@Hydroxyapatite Nanospheres for Highly Efficient Cancer Sonodynamic Immunotherapy
https://orcid.org/0000-0002-6764-0024
AbstractDespite the promise of sonodynamic therapy (SDT)‐mediated immunotherapy, the anticancer efficacy of current sonosensitizers is greatly limited by the immunosuppressive tumor microenvironment (TME) and their inability to selectively respond to it. Herein, oxygen vacancy‐rich MnO2@hydroxyapatite (Ca10(PO4)6(OH)2) core–shell nanospheres (denoted as Ov‐MO@CPO) as an advanced TME‐responsive sonosensitizer for sonodynamic immunotherapy is demonstrated. The Ov‐MO@CPO maintains its structural integrity under neutral conditions but dissolves the pH‐sensitive hydroxyapatite shell under acidic TME to release active oxygen vacancy‐rich MnO2 core, which reinvigorates H2O2 consumption and hypoxia alleviation due to its catalase‐like activity. Furthermore, the introduced oxygen vacancies optimize the electronic structure of Ov‐MO@CPO, with active electronic states near the Fermi level and higher d‐band center. It results in accelerated electron‐hole pair separation and lower catalytic energy barriers to boost ultrasound (US)‐initiated ROS production. These multimodal synergistic effects effectively reverse the immunosuppressive tumor microenvironment, inhibiting tumor growth and metastasis in 4T1 tumor‐bearing mice. No evident toxic effects are observed in normal mouse tissues. Additionally, when combined with an immune checkpoint inhibitor, Ov‐MO@CPO‐mediated SDT further improves the effectiveness of immunotherapy. This work affords a new avenue for developing TME‐dependent sonosensitizers for SDT‐mediated immunotherapy.
Transformable Tumor Microenvironment‐Responsive Oxygen Vacancy‐Rich MnO2@Hydroxyapatite Nanospheres for Highly Efficient Cancer Sonodynamic Immunotherapy
https://orcid.org/0000-0002-6764-0024
AbstractDespite the promise of sonodynamic therapy (SDT)‐mediated immunotherapy, the anticancer efficacy of current sonosensitizers is greatly limited by the immunosuppressive tumor microenvironment (TME) and their inability to selectively respond to it. Herein, oxygen vacancy‐rich MnO2@hydroxyapatite (Ca10(PO4)6(OH)2) core–shell nanospheres (denoted as Ov‐MO@CPO) as an advanced TME‐responsive sonosensitizer for sonodynamic immunotherapy is demonstrated. The Ov‐MO@CPO maintains its structural integrity under neutral conditions but dissolves the pH‐sensitive hydroxyapatite shell under acidic TME to release active oxygen vacancy‐rich MnO2 core, which reinvigorates H2O2 consumption and hypoxia alleviation due to its catalase‐like activity. Furthermore, the introduced oxygen vacancies optimize the electronic structure of Ov‐MO@CPO, with active electronic states near the Fermi level and higher d‐band center. It results in accelerated electron‐hole pair separation and lower catalytic energy barriers to boost ultrasound (US)‐initiated ROS production. These multimodal synergistic effects effectively reverse the immunosuppressive tumor microenvironment, inhibiting tumor growth and metastasis in 4T1 tumor‐bearing mice. No evident toxic effects are observed in normal mouse tissues. Additionally, when combined with an immune checkpoint inhibitor, Ov‐MO@CPO‐mediated SDT further improves the effectiveness of immunotherapy. This work affords a new avenue for developing TME‐dependent sonosensitizers for SDT‐mediated immunotherapy.
Transformable Tumor Microenvironment‐Responsive Oxygen Vacancy‐Rich MnO2@Hydroxyapatite Nanospheres for Highly Efficient Cancer Sonodynamic Immunotherapy
https://orcid.org/0000-0002-6764-0024
AbstractDespite the promise of sonodynamic therapy (SDT)‐mediated immunotherapy, the anticancer efficacy of current sonosensitizers is greatly limited by the immunosuppressive tumor microenvironment (TME) and their inability to selectively respond to it. Herein, oxygen vacancy‐rich MnO2@hydroxyapatite (Ca10(PO4)6(OH)2) core–shell nanospheres (denoted as Ov‐MO@CPO) as an advanced TME‐responsive sonosensitizer for sonodynamic immunotherapy is demonstrated. The Ov‐MO@CPO maintains its structural integrity under neutral conditions but dissolves the pH‐sensitive hydroxyapatite shell under acidic TME to release active oxygen vacancy‐rich MnO2 core, which reinvigorates H2O2 consumption and hypoxia alleviation due to its catalase‐like activity. Furthermore, the introduced oxygen vacancies optimize the electronic structure of Ov‐MO@CPO, with active electronic states near the Fermi level and higher d‐band center. It results in accelerated electron‐hole pair separation and lower catalytic energy barriers to boost ultrasound (US)‐initiated ROS production. These multimodal synergistic effects effectively reverse the immunosuppressive tumor microenvironment, inhibiting tumor growth and metastasis in 4T1 tumor‐bearing mice. No evident toxic effects are observed in normal mouse tissues. Additionally, when combined with an immune checkpoint inhibitor, Ov‐MO@CPO‐mediated SDT further improves the effectiveness of immunotherapy. This work affords a new avenue for developing TME‐dependent sonosensitizers for SDT‐mediated immunotherapy.
Transformable Tumor Microenvironment‐Responsive Oxygen Vacancy‐Rich MnO2@Hydroxyapatite Nanospheres for Highly Efficient Cancer Sonodynamic Immunotherapy
Advanced Science
Li, Minxing (author) / Liu, Qiyu (author) / Xie, Songzuo (author) / Weng, Desheng (author) / He, Jinjun (author) / Yang, Xinyi (author) / Liu, Yuanyuan (author) / You, Jinqi (author) / Liao, Jinghao (author) / Wang, Peng (author)
2025-02-17
Article (Journal)
Electronic Resource
English
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