Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway
Abstract During the treatment of solid tumors, local therapeutic approaches carry the risk of incomplete radical cure, which may lead to rapid tumor growth. Incomplete microwave ablation (iMWA) can induce tumors to exhibit highly invasive and uncontrollable growth, which is related to the immunosupp...
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2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202500670 |
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| author | Yuan Ling Xiayi Liang Kangning Yan Guichun Zeng Xiaoqi Zhu Jinghang Jiang Shaolong Lu Xiaobo Wang Yuying Zhou Zhaoshen Li Wei Mai Duo Wang Jie Chen |
| author_facet | Yuan Ling Xiayi Liang Kangning Yan Guichun Zeng Xiaoqi Zhu Jinghang Jiang Shaolong Lu Xiaobo Wang Yuying Zhou Zhaoshen Li Wei Mai Duo Wang Jie Chen |
| author_sort | Yuan Ling |
| collection | DOAJ |
| description | Abstract During the treatment of solid tumors, local therapeutic approaches carry the risk of incomplete radical cure, which may lead to rapid tumor growth. Incomplete microwave ablation (iMWA) can induce tumors to exhibit highly invasive and uncontrollable growth, which is related to the immunosuppressive microenvironment. A multifunctional bimetallic Ca/Zn nanoagonist (PZH/Zn@CaNA) with a biomimetic liposome‐modified surface to tumor tissues after iMWA is developed. In response to the acidic tumor microenvironment, the released traditional Chinese medicine preparation Pien Tze Huang (PZH) reduced protein expressions of the JAK2‐STAT3 signaling pathway, thereby slowing down the proliferation and growth of hepatocellular carcinoma (HCC). Furthermore, the bimetallic ions Ca2⁺ and Zn2⁺ can cascade to enhance the killing effect of oxidative stress, generating substantial amounts of reactive oxygen species. This process induces pyroptosis and releases significant quantities of damage associated molecular patterns, thereby triggering immune activation mechanisms related to the STING pathway that reshape the immunosuppressive HCC microenvironment resulting from iMWA. This strategy markedly differs from previous chemoimmunotherapies, which not only effectively addressed the problem of conventional drugs showing heterogeneous distribution in tumor regions, but also verified the critical role played by PZH/Zn@CaNA in inhibiting iMWA‐induced rapid tumor growth, regulating oxidative stress and remodeling the immunosuppressive tumor microenvironment. |
| format | Article |
| id | doaj-art-bb0cbb9a1f2d463dbb2cc3730c756590 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-bb0cbb9a1f2d463dbb2cc3730c7565902025-08-20T02:36:40ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.202500670Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling PathwayYuan Ling0Xiayi Liang1Kangning Yan2Guichun Zeng3Xiaoqi Zhu4Jinghang Jiang5Shaolong Lu6Xiaobo Wang7Yuying Zhou8Zhaoshen Li9Wei Mai10Duo Wang11Jie Chen12Department of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaCenter of Interventional Radiology & Vascular Surgery Department of Radiology Zhongda Hospital Medical School Southeast University Nanjing 210009 ChinaDepartment of Hepatobiliary Surgery Department of Medical Ultrasound Department of Traditional Chinese Medicine Guangxi Medical University Cancer Hospital Guangxi Medical University. No. 71 Hedi Road Nanning Guangxi 530021 ChinaAbstract During the treatment of solid tumors, local therapeutic approaches carry the risk of incomplete radical cure, which may lead to rapid tumor growth. Incomplete microwave ablation (iMWA) can induce tumors to exhibit highly invasive and uncontrollable growth, which is related to the immunosuppressive microenvironment. A multifunctional bimetallic Ca/Zn nanoagonist (PZH/Zn@CaNA) with a biomimetic liposome‐modified surface to tumor tissues after iMWA is developed. In response to the acidic tumor microenvironment, the released traditional Chinese medicine preparation Pien Tze Huang (PZH) reduced protein expressions of the JAK2‐STAT3 signaling pathway, thereby slowing down the proliferation and growth of hepatocellular carcinoma (HCC). Furthermore, the bimetallic ions Ca2⁺ and Zn2⁺ can cascade to enhance the killing effect of oxidative stress, generating substantial amounts of reactive oxygen species. This process induces pyroptosis and releases significant quantities of damage associated molecular patterns, thereby triggering immune activation mechanisms related to the STING pathway that reshape the immunosuppressive HCC microenvironment resulting from iMWA. This strategy markedly differs from previous chemoimmunotherapies, which not only effectively addressed the problem of conventional drugs showing heterogeneous distribution in tumor regions, but also verified the critical role played by PZH/Zn@CaNA in inhibiting iMWA‐induced rapid tumor growth, regulating oxidative stress and remodeling the immunosuppressive tumor microenvironment.https://doi.org/10.1002/advs.202500670cellular pyroptosishepatocellular carcinomaincomplete microwave ablationJAK2‐STAT3 signaling pathwaySTING pathway |
| spellingShingle | Yuan Ling Xiayi Liang Kangning Yan Guichun Zeng Xiaoqi Zhu Jinghang Jiang Shaolong Lu Xiaobo Wang Yuying Zhou Zhaoshen Li Wei Mai Duo Wang Jie Chen Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway Advanced Science cellular pyroptosis hepatocellular carcinoma incomplete microwave ablation JAK2‐STAT3 signaling pathway STING pathway |
| title | Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway |
| title_full | Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway |
| title_fullStr | Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway |
| title_full_unstemmed | Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway |
| title_short | Bimetallic Ca/Zn Nanoagonist Remould the Immunosuppressive Hepatocellular Carcinoma Microenvironment Following Incomplete Microwave Ablation via Pyroptosis and the STING Signaling Pathway |
| title_sort | bimetallic ca zn nanoagonist remould the immunosuppressive hepatocellular carcinoma microenvironment following incomplete microwave ablation via pyroptosis and the sting signaling pathway |
| topic | cellular pyroptosis hepatocellular carcinoma incomplete microwave ablation JAK2‐STAT3 signaling pathway STING pathway |
| url | https://doi.org/10.1002/advs.202500670 |
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