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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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Autores principales: Dong, Wenpei, Chen, Mengting, Chang, Chun, Jiang, Tao, Su, Li, Chen, Changpo, Zhang, Guisheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530945/
https://www.ncbi.nlm.nih.gov/pubmed/37762239
http://dx.doi.org/10.3390/ijms241813935
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author Dong, Wenpei
Chen, Mengting
Chang, Chun
Jiang, Tao
Su, Li
Chen, Changpo
Zhang, Guisheng
author_facet Dong, Wenpei
Chen, Mengting
Chang, Chun
Jiang, Tao
Su, Li
Chen, Changpo
Zhang, Guisheng
author_sort Dong, Wenpei
collection PubMed
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.
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spelling pubmed-105309452023-09-28 Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy Dong, Wenpei Chen, Mengting Chang, Chun Jiang, Tao Su, Li Chen, Changpo Zhang, Guisheng Int J Mol Sci Article 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. MDPI 2023-09-11 /pmc/articles/PMC10530945/ /pubmed/37762239 http://dx.doi.org/10.3390/ijms241813935 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dong, Wenpei
Chen, Mengting
Chang, Chun
Jiang, Tao
Su, Li
Chen, Changpo
Zhang, Guisheng
Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS–STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530945/
https://www.ncbi.nlm.nih.gov/pubmed/37762239
http://dx.doi.org/10.3390/ijms241813935
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