Dual-targeted bacterial outer membrane vesicles enhance glioblastoma immunotherapy by regulating tumor microenvironment and inducing IFN-γ-mediated ferroptosis
文献类型：期刊论文
| 作者 | Chen, Chen1,5; Zhu, Xiaojing5; Song, Zefeng2,3,5; Xing, Yutong1,4,5; Jin, Wenrui5; Li, Fan5; Shah, Pir Tariq3; Song, Siqi3,5; Geng, Haoran5; Xu, Kai2 |
| 刊名 | JOURNAL OF NANOBIOTECHNOLOGY
 |
| 出版日期 | 2025-12-12 |
| 卷号 | 24期号:1页码:14 |
| DOI | 10.1186/s12951-025-03922-w |
| 通讯作者 | Wu, Zhenyong(wuzhenyong@simm.ac.cn) |
| 英文摘要 | Glioblastoma (GBM) immunotherapy is limited by the blood-brain barrier (BBB) and the tumor immune resistance. Here, we develop an engineered bacterial outer membrane vesicle (OMV) through safe and straightforward genetic modification of Escherichia coli, termed OMV-C-C, enabling co-expression of cell-penetrating peptides (CPP) and chlorotoxin (CLT) on its surface. The OMV-C-C efficiently crosses BBB and specifically targets tumor cells both in vitro and in vivo. A single intravenous administration of OMV-C-C significantly inhibit GBM growth by enhancing the infiltration of CD8+ T cells in orthotopic brain tumor models. Mechanistically, interferon-gamma (IFN-gamma) released by CD8+ T cells induces ferroptosis-specific lipid peroxidation in tumor cells through inhibiting cystine-glutamate exchanger (system Xc-) and downregulating glutathione peroxidase 4 (GPX4), a pathway demonstrated to be extremely activated in human GBM samples. Furthermore, IFN-gamma facilitates erastin- and RSL-3-induced ferroptosis of tumor cells, particularly in temozolomide (TMZ)-resistant cells. Additionally, OMV-C-C@RSL-3 synergistically suppresses GBM growth in vivo. Thus, biosynthetically engineered OMV-C-C integrates intrinsic immunomodulatory activity with ferroptosis enhancement to strengthen glioblastoma immunotherapies, offering a versatile platform to overcome limitations in brain tumor immunotherapy. |
| 资助项目 | Liaoning Province Clinical Key Specialty Project[2024SZ023] ; Special Supporting Funds for Leading Talents at or Above the Provincial Level in Yantai City[2023000090] ; Natural Science Foundation of Shandong Province[ZR2024QB342] ; China Postdoctoral Science Foundation[2024M763416] ; National Natural Science Foundation of China[32371283] ; Shandong Laboratory Program[SYS202205] ; Key R&D Program of Shandong Province[2024CXPT029] ; Taishan Scholars Program[2023000027] ; Postdoctoral Fellowship Program of CPSF[GZC20241828] ; Dalian Key Medical Specialty Dengfeng Project[2022ZZ210] |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001665198900002 |
| 出版者 | BMC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322676]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Zhenyong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Pudong 201203, Shanghai, Peoples R China 2.Dalian Univ Technol, Dept Spine Surg, Cent Hosp, Dalian 116089, Peoples R China 3.Dalian Univ Technol, Fac Med, Dalian 116024, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Chen,Zhu, Xiaojing,Song, Zefeng,et al. Dual-targeted bacterial outer membrane vesicles enhance glioblastoma immunotherapy by regulating tumor microenvironment and inducing IFN-γ-mediated ferroptosis[J]. JOURNAL OF NANOBIOTECHNOLOGY,2025,24(1):14. |
| APA | Chen, Chen.,Zhu, Xiaojing.,Song, Zefeng.,Xing, Yutong.,Jin, Wenrui.,...&Wu, Zhenyong.(2025).Dual-targeted bacterial outer membrane vesicles enhance glioblastoma immunotherapy by regulating tumor microenvironment and inducing IFN-γ-mediated ferroptosis.JOURNAL OF NANOBIOTECHNOLOGY,24(1),14. |
| MLA | Chen, Chen,et al."Dual-targeted bacterial outer membrane vesicles enhance glioblastoma immunotherapy by regulating tumor microenvironment and inducing IFN-γ-mediated ferroptosis".JOURNAL OF NANOBIOTECHNOLOGY 24.1(2025):14. |
入库方式： OAI收割
来源：上海药物研究所
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