Smart responsive Fe/Mn nanovaccine triggers liver cancer immunotherapy via pyroptosis and pyroptosis-boosted cGAS-STING activation
© 2024. The Author(s)..
BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) remains suboptimal, characterized by high recurrence and metastasis rates. Although metalloimmunotherapy has shown potential in combating tumor proliferation, recurrence and metastasis, current apoptosis-based metalloimmunotherapy fails to elicit sufficient immune response for HCC.
RESULTS: A smart responsive bimetallic nanovaccine was constructed to induce immunogenic cell death (ICD) through pyroptosis and enhance the efficacy of the cGAS-STING pathway. The nanovaccine was composed of manganese-doped mesoporous silica as a carrier, loaded with sorafenib (SOR) and modified with MIL-100 (Fe), where Fe3+, SOR, and Mn2+ were synchronized and released into the tumor with the help of the tumor microenvironment (TME). Afterward, Fe3+ worked synergistically with SOR-induced immunogenic pyroptosis (via both the classical and nonclassical signaling pathways), causing the outflow of abundant immunogenic factors, which contributes to dendritic cell (DC) maturation, and the exposure of double-stranded DNA (dsDNA). Subsequently, the exposed dsDNA and Mn2+ jointly activated the cGAS-STING pathway and induced the release of type I interferons, which further led to DC maturation. Moreover, Mn2+-related T1 magnetic resonance imaging (MRI) was used to visually evaluate the smart response functionality of the nanovaccine.
CONCLUSION: The utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Journal of nanobiotechnology - 22(2024), 1 vom: 06. März, Seite 95 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Du, Qianying [VerfasserIn] |
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| Links: |
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| Themen: |
Bimetallic nanovaccine |
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| Anmerkungen: |
Date Completed 08.03.2024 Date Revised 09.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12951-024-02354-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369387236 |
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| 245 | 1 | 0 | |a Smart responsive Fe/Mn nanovaccine triggers liver cancer immunotherapy via pyroptosis and pyroptosis-boosted cGAS-STING activation |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) remains suboptimal, characterized by high recurrence and metastasis rates. Although metalloimmunotherapy has shown potential in combating tumor proliferation, recurrence and metastasis, current apoptosis-based metalloimmunotherapy fails to elicit sufficient immune response for HCC | ||
| 520 | |a RESULTS: A smart responsive bimetallic nanovaccine was constructed to induce immunogenic cell death (ICD) through pyroptosis and enhance the efficacy of the cGAS-STING pathway. The nanovaccine was composed of manganese-doped mesoporous silica as a carrier, loaded with sorafenib (SOR) and modified with MIL-100 (Fe), where Fe3+, SOR, and Mn2+ were synchronized and released into the tumor with the help of the tumor microenvironment (TME). Afterward, Fe3+ worked synergistically with SOR-induced immunogenic pyroptosis (via both the classical and nonclassical signaling pathways), causing the outflow of abundant immunogenic factors, which contributes to dendritic cell (DC) maturation, and the exposure of double-stranded DNA (dsDNA). Subsequently, the exposed dsDNA and Mn2+ jointly activated the cGAS-STING pathway and induced the release of type I interferons, which further led to DC maturation. Moreover, Mn2+-related T1 magnetic resonance imaging (MRI) was used to visually evaluate the smart response functionality of the nanovaccine | ||
| 520 | |a CONCLUSION: The utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bimetallic nanovaccine | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Magnetic resonance imaging | |
| 650 | 4 | |a Pyroptosis | |
| 650 | 4 | |a cGAS-STING | |
| 650 | 7 | |a Nanovaccines |2 NLM | |
| 700 | 1 | |a Luo, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lian |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Chier |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wenli |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Sijin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhigang |e verfasserin |4 aut | |
| 700 | 1 | |a Ran, Haitao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junrui |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Dajing |e verfasserin |4 aut | |
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