Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma
Abstract Immune checkpoint blockade (ICB) is combined with sonodynamic therapy (SDT) to increase response rates and enhance anticancer efficacy. However, the “always on” property of most sonosensitizers in reducing tumor microenvironment (TME) compromises the therapeutic outcome of sonoimmunotherapy...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409442 |
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| author | Jing Liang Guangwen Cheng Luping Qiu Liyun Xue Huning Xu Xiaohui Qiao Na Guo Huijing Xiang Yu Chen Hong Ding |
| author_facet | Jing Liang Guangwen Cheng Luping Qiu Liyun Xue Huning Xu Xiaohui Qiao Na Guo Huijing Xiang Yu Chen Hong Ding |
| author_sort | Jing Liang |
| collection | DOAJ |
| description | Abstract Immune checkpoint blockade (ICB) is combined with sonodynamic therapy (SDT) to increase response rates and enhance anticancer efficacy. However, the “always on” property of most sonosensitizers in reducing tumor microenvironment (TME) compromises the therapeutic outcome of sonoimmunotherapy and exacerbates adverse side effects. Precisely controllable strategies combining sulfur dioxide (SO2) gas therapy with cancer immunotherapy can address these issues but remain lacking. Herein an “activatable SO2 nanosonosensitizer” for precise sono‐gaseous checkpoint trimodal therapy of orthotopic hepatocellular carcinoma (HCC) is reported, whose full activity is initiated by ultrasound (US) irradiation in the reducing TME. This “activatable SO2 nanosonosensitizer,” Aza‐DNBS nanoparticles (NPs), are established by self‐assembling Aza‐boron‐dipyrromethene based sonosensitizer molecules and 2,4‐dinitrobenzenesulfonate (DNBS)‐caged SO2 prodrug. The activity of Aza‐DNBS NPs is initially silenced, and the sonodynamic, gaseous, and immunosuppressive TME reprogramming activities are precisely awakened under US irradiation. Due to the glutathione‐responsiveness of Aza‐DNBS NPs, Aza‐DNBS NPs can generate large amounts of SO2 for gas therapy‐enhanced SDT, which triggers robust immunogenic cell death activation and reprogramming of the immunosuppressive TME, thereby significantly suppressing orthotopic tumor growth and delaying lung metastasis. Thus, this study represents a strategy for designing a generic nanoplatform for precisely combined immunotherapy of orthotopic HCC. |
| format | Article |
| id | doaj-art-ed311b08a43d43e9b4dadee951ce076e |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ed311b08a43d43e9b4dadee951ce076e2025-02-04T13:14:55ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202409442Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular CarcinomaJing Liang0Guangwen Cheng1Luping Qiu2Liyun Xue3Huning Xu4Xiaohui Qiao5Na Guo6Huijing Xiang7Yu Chen8Hong Ding9Department of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaDepartment of Pathology Zhejiang Cancer Hospital Hangzhou Zhejiang 310022 ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 2000444 ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 2000444 ChinaDepartment of Ultrasound Huashan Hospital Fudan University Shanghai 200040 ChinaAbstract Immune checkpoint blockade (ICB) is combined with sonodynamic therapy (SDT) to increase response rates and enhance anticancer efficacy. However, the “always on” property of most sonosensitizers in reducing tumor microenvironment (TME) compromises the therapeutic outcome of sonoimmunotherapy and exacerbates adverse side effects. Precisely controllable strategies combining sulfur dioxide (SO2) gas therapy with cancer immunotherapy can address these issues but remain lacking. Herein an “activatable SO2 nanosonosensitizer” for precise sono‐gaseous checkpoint trimodal therapy of orthotopic hepatocellular carcinoma (HCC) is reported, whose full activity is initiated by ultrasound (US) irradiation in the reducing TME. This “activatable SO2 nanosonosensitizer,” Aza‐DNBS nanoparticles (NPs), are established by self‐assembling Aza‐boron‐dipyrromethene based sonosensitizer molecules and 2,4‐dinitrobenzenesulfonate (DNBS)‐caged SO2 prodrug. The activity of Aza‐DNBS NPs is initially silenced, and the sonodynamic, gaseous, and immunosuppressive TME reprogramming activities are precisely awakened under US irradiation. Due to the glutathione‐responsiveness of Aza‐DNBS NPs, Aza‐DNBS NPs can generate large amounts of SO2 for gas therapy‐enhanced SDT, which triggers robust immunogenic cell death activation and reprogramming of the immunosuppressive TME, thereby significantly suppressing orthotopic tumor growth and delaying lung metastasis. Thus, this study represents a strategy for designing a generic nanoplatform for precisely combined immunotherapy of orthotopic HCC.https://doi.org/10.1002/advs.202409442gas therapyimmunotherapynanomedicinenanosonosensitizersonodynamic therapy |
| spellingShingle | Jing Liang Guangwen Cheng Luping Qiu Liyun Xue Huning Xu Xiaohui Qiao Na Guo Huijing Xiang Yu Chen Hong Ding Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma Advanced Science gas therapy immunotherapy nanomedicine nanosonosensitizer sonodynamic therapy |
| title | Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma |
| title_full | Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma |
| title_fullStr | Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma |
| title_full_unstemmed | Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma |
| title_short | Activatable Sulfur Dioxide Nanosonosensitizer Enables Precisely Controllable Sono‐Gaseous Checkpoint Trimodal Therapy for Orthotopic Hepatocellular Carcinoma |
| title_sort | activatable sulfur dioxide nanosonosensitizer enables precisely controllable sono gaseous checkpoint trimodal therapy for orthotopic hepatocellular carcinoma |
| topic | gas therapy immunotherapy nanomedicine nanosonosensitizer sonodynamic therapy |
| url | https://doi.org/10.1002/advs.202409442 |
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