Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy
Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13935 |
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| author | Wenpei Dong Mengting Chen Chun Chang Tao Jiang Li Su Changpo Chen Guisheng Zhang |
| author_facet | Wenpei Dong Mengting Chen Chun Chang Tao Jiang Li Su Changpo Chen Guisheng Zhang |
| author_sort | Wenpei Dong |
| collection | DOAJ |
| description | Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2′,3′-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity. In this work, Co,N-doped carbon dots (CoNCDs) were used as a model nanozyme to evaluate the properties of the anti-tumor mechanism, and effective inhibition of S180 tumor was achieved. Based on CoNCDs’ good biocompatibility and therapeutic effect on the tumor, we then introduced the cGAS–STING agonist, and the combination of the CoNCDs and STING agonist significantly inhibited tumor growth, and no significant systemic toxicity was observed. The combined system achieved the enhanced tumor synergistic immunotherapy through TME reprogramming via the peroxidase-like activity of the CoNCDs and cGAS–STING signaling pathway agonist synergistically. Our work provides not only a new effective way to reprogram TME in vivo, but also a promising synergic antitumor therapy strategy. |
| first_indexed | 2024-03-10T22:39:57Z |
| format | Article |
| id | doaj.art-17fb825351864e0eab9185d102117781 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:57Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-17fb825351864e0eab9185d1021177812023-11-19T11:05:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181393510.3390/ijms241813935Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer ImmunotherapyWenpei Dong0Mengting Chen1Chun Chang2Tao Jiang3Li Su4Changpo Chen5Guisheng Zhang6Electronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaElectronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, ChinaNanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2′,3′-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity. In this work, Co,N-doped carbon dots (CoNCDs) were used as a model nanozyme to evaluate the properties of the anti-tumor mechanism, and effective inhibition of S180 tumor was achieved. Based on CoNCDs’ good biocompatibility and therapeutic effect on the tumor, we then introduced the cGAS–STING agonist, and the combination of the CoNCDs and STING agonist significantly inhibited tumor growth, and no significant systemic toxicity was observed. The combined system achieved the enhanced tumor synergistic immunotherapy through TME reprogramming via the peroxidase-like activity of the CoNCDs and cGAS–STING signaling pathway agonist synergistically. Our work provides not only a new effective way to reprogram TME in vivo, but also a promising synergic antitumor therapy strategy.https://www.mdpi.com/1422-0067/24/18/13935cancer immunotherapycGAS/STINGCo,N-doped carbon dotsnanozymes |
| spellingShingle | Wenpei Dong Mengting Chen Chun Chang Tao Jiang Li Su Changpo Chen Guisheng Zhang Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy International Journal of Molecular Sciences cancer immunotherapy cGAS/STING Co,N-doped carbon dots nanozymes |
| title | Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy |
| title_full | Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy |
| title_fullStr | Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy |
| title_full_unstemmed | Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy |
| title_short | Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy |
| title_sort | remodeling of tumor microenvironment by nanozyme combined cgas sting signaling pathway agonist for enhancing cancer immunotherapy |
| topic | cancer immunotherapy cGAS/STING Co,N-doped carbon dots nanozymes |
| url | https://www.mdpi.com/1422-0067/24/18/13935 |
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