M-MDSCs mediated trans-BBB drug delivery for suppression of glioblastoma recurrence post-standard treatment
Copyright © 2023. Published by Elsevier B.V..
We found that immunosuppressive monocytic-myeloid-derived suppressor cells (M-MDSCs) were more likely to be recruited by glioblastoma (GBM) through adhesion molecules on GBM-associated endothelial cells upregulated post-chemoradiotherapy. These cells are continuously generated during tumor progression, entering tumors and expressing PD-L1 at a high level, allowing GBM to exhaust T cells and evade attack from the immune system, thereby facilitating GBM relapse. αLy-6C-LAMP is composed of (i) drug cores with slightly negative charges condensed by cationic protamine and plasmids encoding PD-L1 trap protein, (ii) pre-formulated cationic liposomes targeted to Ly-6C for encapsulating the drug cores, and (iii) a layer of red blood cell membrane on the surface for effectuating long-circulation. αLy-6C-LAMP persistently targets peripheral, especially splenic, M-MDSCs and delivers secretory PD-L1 trap plasmids, leveraging M-MDSCs to transport the plasmids crossing the blood-brain barrier (BBB), thus expressing PD-L1 trap protein in tumors to inhibit PD-1/PD-L1 pathway. Our proposed drug delivery strategy involving intermediaries presents an efficient cross-BBB drug delivery concept that incorporates live-cell targeting and long-circulating nanotechnology to address GBM recurrence.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:369 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 369(2024) vom: 28. März, Seite 199-214 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Tong [VerfasserIn] |
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| Links: |
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| Themen: |
Blood-brain barrier |
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| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.jconrel.2024.03.043 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370272560 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a We found that immunosuppressive monocytic-myeloid-derived suppressor cells (M-MDSCs) were more likely to be recruited by glioblastoma (GBM) through adhesion molecules on GBM-associated endothelial cells upregulated post-chemoradiotherapy. These cells are continuously generated during tumor progression, entering tumors and expressing PD-L1 at a high level, allowing GBM to exhaust T cells and evade attack from the immune system, thereby facilitating GBM relapse. αLy-6C-LAMP is composed of (i) drug cores with slightly negative charges condensed by cationic protamine and plasmids encoding PD-L1 trap protein, (ii) pre-formulated cationic liposomes targeted to Ly-6C for encapsulating the drug cores, and (iii) a layer of red blood cell membrane on the surface for effectuating long-circulation. αLy-6C-LAMP persistently targets peripheral, especially splenic, M-MDSCs and delivers secretory PD-L1 trap plasmids, leveraging M-MDSCs to transport the plasmids crossing the blood-brain barrier (BBB), thus expressing PD-L1 trap protein in tumors to inhibit PD-1/PD-L1 pathway. Our proposed drug delivery strategy involving intermediaries presents an efficient cross-BBB drug delivery concept that incorporates live-cell targeting and long-circulating nanotechnology to address GBM recurrence | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Blood-brain barrier | |
| 650 | 4 | |a Drug delivery | |
| 650 | 4 | |a Glioblastoma | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a M-MDSCs | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yupeng |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Fuqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hong |e verfasserin |4 aut | |
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