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Albofungin vesicle nanobombs trigger lysosomal disruption for self-enhanced pyroptosis and cGAS-STING pathway activation in glioblastoma immunotherapy

文献类型：期刊论文

作者Chen, Chen1,5; Tan, Shuai5; Zhu, Xiaojing5; Song, Zefeng4,5; Xing, Yutong1,3,5; Jin, Wenrui5; Xu, Jingyi1,3,5; Song, Siqi4,5; Geng, Haoran5; Chen, Xingyu2,5
刊名JOURNAL OF CONTROLLED RELEASE
出版日期2026-04-10
卷号392页码:14
关键词Outer membrane vesicles Lysosomal disruption Pyroptosis cGAS-STING Immunotherapy
ISSN号0168-3659
DOI10.1016/j.jconrel.2026.114718
通讯作者Huang, Chunshuai(huangchunshuai@simm.ac.cn) ; Wu, Zhenyong(wuzhenyong@simm.ac.cn)
英文摘要Glioblastoma (GBM) remains one of the most intractable malignancies owing to the dual challenges of the blood brain barrier (BBB) and profound immunosuppression. Here, we present a nanobomb (OMV-ApoE@ALF) that integrates heterologous production of the aromatic polyketide albofungin (ALF) with programmable outer membrane vesicles (OMVs) displaying ApoE peptides for GBM immunotherapy. OMV-ApoE@ALF efficiently crossed the BBB, accumulated in tumors, and functioned as a lysosomal nanobomb to boost pyroptosis and activate cGAS-STING pathway, thereby promoting dendritic cell maturation, T-cell infiltration, and durable antitumor immunity. Mechanistically, OMV-ApoE@ALF delivered ALF into lysosomes, inducing lysosomal disruption, reactive oxygen species (ROS) production, and subsequent mitochondrial damage. Crucially, this lysosomal rupture also suppressed protective autophagy of tumor cells themselves, thereby reinforcing the cascade activation between caspase-3/GSDME-dependent pyroptosis and cGAS-STING signaling pathway. This lysosomal disruption-nanobomb represents a new strategy for advancing GBM immunotherapy.
WOS关键词CLEAVAGE
资助项目Key R & D Program of Shandong Province[2024CXPT029] ; Key R & D Program of Shandong Province[2025CXPT012] ; National Natural Science Foundation of China[32371283] ; National Natural Science Foundation of China[22407132] ; Taishan Scholars Program[2023000027] ; Taishan Scholars Program[tsqn202408316] ; Postdoctoral Fellowship Program of CPSF[GZC20241828] ; China Postdoctoral Science Foundation[2024M763416] ; Shandong Provincial Natural Science Fund for Excellent Young Scientists Fund Program (Overseas)[2025HWYQ-069] ; Shandong Provincial Natural Science Foundation[ZR2024QB342] ; Shandong Provincial Natural Science Foundation[ZR2024QC204] ; Shanghai Pujiang Program[23PJ1415100] ; Shandong Laboratory Program[SYS202205] ; Special Supporting Funds for Leading Talents at or Above the Provincial Level in Yantai City[2023000090]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001693405100001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/323038]  
专题中国科学院上海药物研究所
通讯作者Huang, Chunshuai; Wu, Zhenyong
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Jiangxi Normal Univ, Coll Life Sci, Nanchang 330022, Jiangxi, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Dalian Univ Technol, Fac Med, Dalian 116024, 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,Tan, Shuai,Zhu, Xiaojing,et al. Albofungin vesicle nanobombs trigger lysosomal disruption for self-enhanced pyroptosis and cGAS-STING pathway activation in glioblastoma immunotherapy[J]. JOURNAL OF CONTROLLED RELEASE,2026,392:14.
APA Chen, Chen.,Tan, Shuai.,Zhu, Xiaojing.,Song, Zefeng.,Xing, Yutong.,...&Wu, Zhenyong.(2026).Albofungin vesicle nanobombs trigger lysosomal disruption for self-enhanced pyroptosis and cGAS-STING pathway activation in glioblastoma immunotherapy.JOURNAL OF CONTROLLED RELEASE,392,14.
MLA Chen, Chen,et al."Albofungin vesicle nanobombs trigger lysosomal disruption for self-enhanced pyroptosis and cGAS-STING pathway activation in glioblastoma immunotherapy".JOURNAL OF CONTROLLED RELEASE 392(2026):14.

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来源：上海药物研究所

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