An Immunocompetent Hafnium Oxide-Based STING Nanoagonist for Cancer Radio-immunotherapy
cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
ACS nano - 18(2024), 5 vom: 06. Feb., Seite 4189-4204 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Yuhua [VerfasserIn] |
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| Links: |
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| Themen: |
3C4Z4KG52T |
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| Anmerkungen: |
Date Completed 07.02.2024 Date Revised 07.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acsnano.3c09293 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a cGAS-STING signaling plays a critical role in radiotherapy (RT)-mediated immunomodulation. However, RT alone is insufficient to sustain STING activation in tumors under a safe X-ray dose. Here, we propose a radiosensitization cooperated with cGAS stimulation strategy by engineering a core-shell structured nanosized radiosensitizer-based cGAS-STING agonist, which is constituted with the hafnium oxide (HfO2) core and the manganese oxide (MnO2) shell. HfO2-mediated radiosensitization enhances immunogenic cell death to afford tumor associated antigens and adequate cytosolic dsDNA, while the GSH-degradable MnO2 sustainably releases Mn2+ in tumors to improve the recognition sensitization of cGAS. The synchronization of sustained Mn2+ supply with cumulative cytosolic dsDNA damage synergistically augments the cGAS-STING activation in irradiated tumors, thereby enhancing RT-triggered local and system effects when combined with an immune checkpoint inhibitor. Therefore, the synchronous radiosensitization with sustained STING activation is demonstrated as a potent immunostimulation strategy to optimize cancer radio-immuotherapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hafnium oxide | |
| 650 | 4 | |a Immunostimulation | |
| 650 | 4 | |a Radio-immunotherapy | |
| 650 | 4 | |a Radiosensitization | |
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| 700 | 1 | |a Ding, Shuaishuai |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Yunping |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Lijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jingrong |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Qinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Ruili |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Guangjie |e verfasserin |4 aut | |
| 700 | 1 | |a Bian, Xiu-Wu |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Gan |e verfasserin |4 aut | |
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