Angiopep-2-decorated bacterial outer membrane vesicles penetrate the blood-brain barrier for glioblastoma chemo-immunotherapy.
Overview
- Core Laboratory, Qingdao Central Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China
- Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong province, China
- Faculty of Medicine, School of Basic Medical Sciences, Dalian University of Technology, Dalian, Liaoning Province, China
- Department of Neurosurgery, Peking University Third Hospital, Beijing, China
- Center for Precision Neurosurgery and Oncology, Peking University Health Science Center, Beijing, China
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Abstract
Glioblastoma (GBM) therapy remains one of the most formidable challenges in oncology because of the blood-brain barrier (BBB), immunosuppressive tumor microenvironment, and drug resistance. To overcome these challenges, we designed engineered angiopep-2-decorated bacterial outer membrane vesicles for targeted drug delivery across the BBB. Using a novel autotransporter-based (AIDA-I) genetic engineering approach, we developed a novel platform via straightforward genetic modification of E. coli with our designed pAIDA1-ANG plasmid to stably display Angiopep-2 on OMVs (OMV-ANG) for targeted BBB penetration via LDL receptor-related protein 1 (LRP1) receptor-mediated transcytosis. Our in vitro BBB model and real-time in vivo imaging confirmed the BBB penetration and transcytosis of OMV-ANG and doxorubicin-loaded OMV-ANG, with accelerated brain accumulation within 2–4 h post-injection and sustained retention for 6 h. In orthotopic GBM models, systemic DOX-OMV-ANG administration extended survival, induced potent tumor suppression via DOX-induced apoptosis and OMV-ANG-mediated immunomodulation, and triggered sustained IFN-γ elevation with macrophage and CD8 + T-cell recruitment. This engineered OMV-ANG platform shows promise in overcoming critical therapeutic barriers in glioblastoma and warrants further investigation as a versatile delivery system for diverse CNS therapeutics.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Datasets cited
- figshare:32039911, at figshare; found in DataCite
Data availability statement
The data that support the findings of this research are available from the corresponding author, WCJ, upon reasonable request.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 6 keywords, 13 MeSH terms, 4 funders, 62 references.
Cite
This paper
Shah, P. T., Lou, Z., Zhu, X., Jin, W., Chen, C., Hu, T., Guo, P., Zhao, X., Li, F., Xiaoliang, Y., Wu, Z., & Wu, C. (2026). Angiopep-2-decorated bacterial outer membrane vesicles penetrate the blood-brain barrier for glioblastoma chemo-immunotherapy. Drug delivery, 33(1), 2660007. https://
BibTeX
@article{shah2026angiope
author = {Shah, Pir Tariq and Lou, Zhangrong and Zhu, Xiaojing and Jin, Wenrui and Chen, Chen and Hu, Tao and Guo, Peng and Zhao, Xuanzhu and Li, Fan and Xiaoliang, Yin and Wu, Zhenyong and Wu, Chengjun},
title = {{Angiopep-2-decorated bacterial outer membrane vesicles penetrate the blood-brain barrier for glioblastoma chemo-immunotherapy}},
journal = {Drug delivery},
year = {2026},
month = apr,
volume = {33},
number = {1},
pages = {2660007},
publisher = {Taylor \& Francis},
issn = {1071-7544},
doi = {10.1080/
url = {https://
pmid = {41992448},
pmcid = {PMC13094214}
}
RIS
TY - JOUR
AU - Shah, Pir Tariq
AU - Lou, Zhangrong
AU - Zhu, Xiaojing
AU - Jin, Wenrui
AU - Chen, Chen
AU - Hu, Tao
AU - Guo, Peng
AU - Zhao, Xuanzhu
AU - Li, Fan
AU - Xiaoliang, Yin
AU - Wu, Zhenyong
AU - Wu, Chengjun
TI - Angiopep-2-decorated bacterial outer membrane vesicles penetrate the blood-brain barrier for glioblastoma chemo-immunotherapy
T2 - Drug delivery
J2 - Drug Deliv
PY - 2026
DA - 2026/
VL - 33
IS - 1
SP - 2660007
SN - 1071-7544
PB - Taylor & Francis
DO - 10.1080/
UR - https://
LA - en
ER -
CSL-JSON
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