A T-Cell Inspired Sonoporation System Enhances Low-Dose X-Ray-Mediated Pyroptosis and Radioimmunotherapy Efficacy by Restoring Gasdermin-E Expression
© 2024 Wiley‐VCH GmbH..
Genome editing has the potential to improve the unsatisfactory therapeutic effect of antitumor immunotherapy. However, the cell plasma membrane prevents the entry of almost all free genome-manipulation agents. Therefore, a system can be spatiotemporally controlled and can instantly open the cellular membrane to allow the entry of genome-editing agents into target cells is needed. Here, inspired by the ability of T cells to deliver cytotoxins to cancer cells by perforation, an ultrasound (US)-controlled perforation system (UPS) is established to enhance the delivery of free genome-manipulating agents. The UPS can perforate the tumor cell membrane while maintaining cell viability via a controllable lipid peroxidation reaction. In vitro, transmembrane-incapable plasmids can enter cells and perform genome editing with the assistance of UPS, achieving an efficiency of up to 90%. In vivo, the UPS is biodegradable, nonimmunogenic, and tumor-targeting, enabling the puncturing of tumor cells under US. With the application of UPS-assisted genome editing, gasdermin-E expression in 4T1 tumor-bearing mice is successfully restored, which leads to pyroptosis-mediated antitumor immunotherapy via low-dose X-ray irradiation. This study provides new insights for designing a sonoporation system for genome editing. Moreover, the results demonstrate that restoring gasdermin expression by genome editing significantly improves the efficacy of radioimmunotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Advanced materials (Deerfield Beach, Fla.) - (2024) vom: 24. März, Seite e2401384 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yin, Hao [VerfasserIn] |
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| Links: |
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| Themen: |
Genome editing |
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| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/adma.202401384 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370115465 |
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| 520 | |a Genome editing has the potential to improve the unsatisfactory therapeutic effect of antitumor immunotherapy. However, the cell plasma membrane prevents the entry of almost all free genome-manipulation agents. Therefore, a system can be spatiotemporally controlled and can instantly open the cellular membrane to allow the entry of genome-editing agents into target cells is needed. Here, inspired by the ability of T cells to deliver cytotoxins to cancer cells by perforation, an ultrasound (US)-controlled perforation system (UPS) is established to enhance the delivery of free genome-manipulating agents. The UPS can perforate the tumor cell membrane while maintaining cell viability via a controllable lipid peroxidation reaction. In vitro, transmembrane-incapable plasmids can enter cells and perform genome editing with the assistance of UPS, achieving an efficiency of up to 90%. In vivo, the UPS is biodegradable, nonimmunogenic, and tumor-targeting, enabling the puncturing of tumor cells under US. With the application of UPS-assisted genome editing, gasdermin-E expression in 4T1 tumor-bearing mice is successfully restored, which leads to pyroptosis-mediated antitumor immunotherapy via low-dose X-ray irradiation. This study provides new insights for designing a sonoporation system for genome editing. Moreover, the results demonstrate that restoring gasdermin expression by genome editing significantly improves the efficacy of radioimmunotherapy | ||
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| 650 | 4 | |a genome editing | |
| 650 | 4 | |a low‐dose X‐ray | |
| 650 | 4 | |a pyroptosis | |
| 650 | 4 | |a radioimmunotherapy | |
| 700 | 1 | |a Hu, Xiaoqu |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Congying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yida |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Hanqian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Wenting |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Danli |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qinyang |e verfasserin |4 aut | |
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