Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment

Yanjun Lu,1,* Zhiyan Li,2,* Xudong Zhu,1 Qingwei Zeng,1 Song Liu,1 Wenxian Guan1 1Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Division of T...

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Main Authors: Lu Y, Li Z, Zhu X, Zeng Q, Liu S, Guan W
Format: Article
Language:English
Published: Dove Medical Press 2025-01-01
Series:International Journal of Nanomedicine
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Online Access:https://www.dovepress.com/novel-modifications-and-delivery-modes-of-cyclic-dinucleotides-for-sti-peer-reviewed-fulltext-article-IJN
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author Lu Y
Li Z
Zhu X
Zeng Q
Liu S
Guan W
author_facet Lu Y
Li Z
Zhu X
Zeng Q
Liu S
Guan W
author_sort Lu Y
collection DOAJ
description Yanjun Lu,1,* Zhiyan Li,2,* Xudong Zhu,1 Qingwei Zeng,1 Song Liu,1 Wenxian Guan1 1Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Division of Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Liu; Wenxian Guan, Email liusong@nju.edu.cn; guan_wenxian@sina.comAbstract: The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability to activate tumor-specific immune responses for tumor killing. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune pathway that activates antitumor immunity by producing type I interferons. Cyclic dinucleotides (CDNs), produced by cGAS sensing cytoplasmic abnormal DNA, are major intermediate activating molecules in the STING pathway. Nowadays, CDNs and their derivatives have widely worked as powerful STING agonists in tumor immunotherapy. However, their clinical translation is hindered by the negative electrical properties, sensitivity to hydrolytic enzymes, and systemic toxicity. Recently, various CDN delivery systems have made significant progress in addressing these issues, either through monotherapy or in combination with other treatment modalities. This review details recent advances in CDNs-based pharmaceutical development or delivery strategies for enriching CDNs at tumor sites and activating the STING pathway.Keywords: cyclic dinucleotides, stimulator of interferon genes pathway, immunotherapy
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series International Journal of Nanomedicine
spelling doaj-art-02a74cca971d42f49b040fd9842179db2025-01-07T16:42:39ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-01-01Volume 2018119798956Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer TreatmentLu YLi ZZhu XZeng QLiu SGuan WYanjun Lu,1,* Zhiyan Li,2,* Xudong Zhu,1 Qingwei Zeng,1 Song Liu,1 Wenxian Guan1 1Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Division of Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Song Liu; Wenxian Guan, Email liusong@nju.edu.cn; guan_wenxian@sina.comAbstract: The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability to activate tumor-specific immune responses for tumor killing. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune pathway that activates antitumor immunity by producing type I interferons. Cyclic dinucleotides (CDNs), produced by cGAS sensing cytoplasmic abnormal DNA, are major intermediate activating molecules in the STING pathway. Nowadays, CDNs and their derivatives have widely worked as powerful STING agonists in tumor immunotherapy. However, their clinical translation is hindered by the negative electrical properties, sensitivity to hydrolytic enzymes, and systemic toxicity. Recently, various CDN delivery systems have made significant progress in addressing these issues, either through monotherapy or in combination with other treatment modalities. This review details recent advances in CDNs-based pharmaceutical development or delivery strategies for enriching CDNs at tumor sites and activating the STING pathway.Keywords: cyclic dinucleotides, stimulator of interferon genes pathway, immunotherapyhttps://www.dovepress.com/novel-modifications-and-delivery-modes-of-cyclic-dinucleotides-for-sti-peer-reviewed-fulltext-article-IJNcyclic dinucleotidesstimulator of interferon genes pathwayimmunotherapy.
spellingShingle Lu Y
Li Z
Zhu X
Zeng Q
Liu S
Guan W
Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
International Journal of Nanomedicine
cyclic dinucleotides
stimulator of interferon genes pathway
immunotherapy.
title Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
title_full Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
title_fullStr Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
title_full_unstemmed Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
title_short Novel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment
title_sort novel modifications and delivery modes of cyclic dinucleotides for sting activation in cancer treatment
topic cyclic dinucleotides
stimulator of interferon genes pathway
immunotherapy.
url https://www.dovepress.com/novel-modifications-and-delivery-modes-of-cyclic-dinucleotides-for-sti-peer-reviewed-fulltext-article-IJN
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