Metal-organic framework nanoagent induces cuproptosis for effective immunotherapy of malignant glioblastoma

Glioblastoma (GBM) is an aggressive brain cancer with an immunosuppressive tumor microenvironment. Here, a copper-based nanoplatform BSO-CAT@MOF-199 @DDM (BCMD) is constructed for mediating cuproptosis and subsequently promoting immunotherapy of glioblastoma. Specifically, BCMD can be degraded in th...

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Bibliographic Details
Published in:Nano today Vol. 51; p. 101911
Main Authors: Huang, Qian-Xiao, Liang, Jun-Long, Chen, Qi-Wen, Jin, Xiao-Kang, Niu, Mei-Ting, Dong, Cheng-Yuan, Zhang, Xian-Zheng
Format: Journal Article
Language:English
Published: Elsevier Ltd 01.08.2023
Subjects:
Cuproptosis
Ferredoxin
Glioblastoma
Immunogenic cell death
Intranasal administration
Intranasal administration
Ferredoxin
Cuproptosis
Immunogenic cell death
Glioblastoma
ISSN:1748-0132, 1878-044X
Online Access:Get full text
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Summary:Glioblastoma (GBM) is an aggressive brain cancer with an immunosuppressive tumor microenvironment. Here, a copper-based nanoplatform BSO-CAT@MOF-199 @DDM (BCMD) is constructed for mediating cuproptosis and subsequently promoting immunotherapy of glioblastoma. Specifically, BCMD can be degraded in the slightly acidic tumor environment to release Cu2+, which will be further reduced to toxic Cu+ to induce cuproptosis under the regulation of high level of ferredoxin 1 (FDX1). Meanwhile, buthionine-sulfoximine (BSO) and catalase (CAT) released from BCMD can reduce the glutathione (GSH) synthesis and increase O2 content in tumor cells, thereby rendering the tumor cells more sensitive to BCMD-mediated cuproptosis. In vivo experiments show that BCMD mediated cuproptosis can trigger the immunogenic cell death (ICD) to increase the infiltration of cytotoxic T lymphocytes and reverse the immunosuppressive microenvironment of glioblastoma to enhance tumoricidal immunity. Furthermore, anti-tumor therapeutic efficiency of immune checkpoint blockade (ICB) therapy is significantly enhanced by combining BCMD with αPD-L1. [Display omitted] •Served as a non-invasive nasal administration preparation to bypass blood brain barrier and reduce systemic side effects.•Induced cuproptosis under the regulation of high level of ferredoxin 1 (FDX1) in glioblastoma.•Reversed the immunosuppressive tumor microenvironment to enhance effective anti-tumor effect.•Good biological safety and clinical application prospect.
ISSN:1748-0132
1878-044X
DOI:10.1016/j.nantod.2023.101911