Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma
Abstract Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release Hy...
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| Format: | Article |
| Language: | English |
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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.202408323 |
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| author | Hao Yu Wenjing Liu Kaikai Ding Jiangjie Wu Cheng Wang Siyuan Wang Lingyun Wu Qiuying Tang Xin Yin Kan Jiang Danfang Yan Xu Wang Si Chen Senxiang Yan |
| author_facet | Hao Yu Wenjing Liu Kaikai Ding Jiangjie Wu Cheng Wang Siyuan Wang Lingyun Wu Qiuying Tang Xin Yin Kan Jiang Danfang Yan Xu Wang Si Chen Senxiang Yan |
| author_sort | Hao Yu |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release HydroLipo System (SRHLS) is developed, in which hydrogels and nanoparticles are combined for controlled drug release. The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM. |
| format | Article |
| id | doaj-art-a68432655dcf46deb2f1a3d2ddaa750a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a68432655dcf46deb2f1a3d2ddaa750a2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202408323Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in GlioblastomaHao Yu0Wenjing Liu1Kaikai Ding2Jiangjie Wu3Cheng Wang4Siyuan Wang5Lingyun Wu6Qiuying Tang7Xin Yin8Kan Jiang9Danfang Yan10Xu Wang11Si Chen12Senxiang Yan13Department of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaCollege of Materials Science and Engineering Zhejiang Key Laboratory of Plastic Modification and Processing Technology Zhejiang University of Technology Hangzhou 310014 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaCollege of Materials Science and Engineering Zhejiang Key Laboratory of Plastic Modification and Processing Technology Zhejiang University of Technology Hangzhou 310014 P. R. ChinaCollege of Materials Science and Engineering Zhejiang Key Laboratory of Plastic Modification and Processing Technology Zhejiang University of Technology Hangzhou 310014 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaCollege of Materials Science and Engineering Zhejiang Key Laboratory of Plastic Modification and Processing Technology Zhejiang University of Technology Hangzhou 310014 P. R. ChinaCollege of Materials Science and Engineering Zhejiang Key Laboratory of Plastic Modification and Processing Technology Zhejiang University of Technology Hangzhou 310014 P. R. ChinaDepartment of Radiation Oncology the First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Road Hangzhou Zhejiang 310003 P. R. ChinaAbstract Glioblastoma (GBM) remains a daunting oncological challenge because of its aggressive nature and resistance to conventional therapies. Inhibition of the intrinsic STING pathway in GBM hampers the effectiveness of immunotherapies. To overcome this clinical limitation, a Sequential Release HydroLipo System (SRHLS) is developed, in which hydrogels and nanoparticles are combined for controlled drug release. The SRHLS sequentially released decitabine and STING agonists, thereby correcting STING signaling dysfunction through epigenetic reprogramming and enhancing antitumor immunity. According to in vitro and in vivo experiments, the SRHLS reshaped the tumor microenvironment and markedly inhibited tumor growth, recurrence, and metastasis. These findings underscore the potential of the SRHLS as a promising therapeutic strategy for GBM.https://doi.org/10.1002/advs.202408323epigenetic reprogrammingglioblastomasequential release hydroLipo systemSTING |
| spellingShingle | Hao Yu Wenjing Liu Kaikai Ding Jiangjie Wu Cheng Wang Siyuan Wang Lingyun Wu Qiuying Tang Xin Yin Kan Jiang Danfang Yan Xu Wang Si Chen Senxiang Yan Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma Advanced Science epigenetic reprogramming glioblastoma sequential release hydroLipo system STING |
| title | Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma |
| title_full | Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma |
| title_fullStr | Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma |
| title_full_unstemmed | Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma |
| title_short | Sequential Release HydroLipo System for STING Gene Epigenetic Reprogramming and Immune Activation in Glioblastoma |
| title_sort | sequential release hydrolipo system for sting gene epigenetic reprogramming and immune activation in glioblastoma |
| topic | epigenetic reprogramming glioblastoma sequential release hydroLipo system STING |
| url | https://doi.org/10.1002/advs.202408323 |
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