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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| Vydáno v: | Nano today Ročník 51; s. 101911 |
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| Hlavní autoři: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Elsevier Ltd
01.08.2023
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| Témata: | |
| ISSN: | 1748-0132, 1878-044X |
| On-line přístup: | Získat plný text |
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| Abstract | 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.
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•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. |
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| AbstractList | 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. |
| ArticleNumber | 101911 |
| Author | Niu, Mei-Ting Dong, Cheng-Yuan Huang, Qian-Xiao Chen, Qi-Wen Jin, Xiao-Kang Liang, Jun-Long Zhang, Xian-Zheng |
| Author_xml | – sequence: 1 givenname: Qian-Xiao surname: Huang fullname: Huang, Qian-Xiao organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China – sequence: 2 givenname: Jun-Long surname: Liang fullname: Liang, Jun-Long organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China – sequence: 3 givenname: Qi-Wen surname: Chen fullname: Chen, Qi-Wen organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China – sequence: 4 givenname: Xiao-Kang surname: Jin fullname: Jin, Xiao-Kang organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China – sequence: 5 givenname: Mei-Ting surname: Niu fullname: Niu, Mei-Ting organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China – sequence: 6 givenname: Cheng-Yuan surname: Dong fullname: Dong, Cheng-Yuan email: dongchengyuan@wchscu.cn organization: Department of Neurosurgery & Laboratory of Neurosurgery West China Hospital Sichuan University, Chengdu 610041, PR China – sequence: 7 givenname: Xian-Zheng orcidid: 0000-0001-6242-6005 surname: Zhang fullname: Zhang, Xian-Zheng email: xz-zhang@whu.edu.cn organization: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China |
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| Keywords | Intranasal administration Ferredoxin Cuproptosis Immunogenic cell death Glioblastoma |
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