Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy
The cGAS-STING pathway holds tremendous potential as a regulator of immune responses, offering a means to reshape the tumor microenvironment and enhance tumor immunotherapy. Despite the emergence of STING agonists, their clinical viability is hampered by stability and delivery challenges, as well as...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424000772 |
| _version_ | 1797260355508895744 |
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| author | Yingcai Meng Jiaxin Huang Jinsong Ding Haiyan Zhou Yong Li Wenhu Zhou |
| author_facet | Yingcai Meng Jiaxin Huang Jinsong Ding Haiyan Zhou Yong Li Wenhu Zhou |
| author_sort | Yingcai Meng |
| collection | DOAJ |
| description | The cGAS-STING pathway holds tremendous potential as a regulator of immune responses, offering a means to reshape the tumor microenvironment and enhance tumor immunotherapy. Despite the emergence of STING agonists, their clinical viability is hampered by stability and delivery challenges, as well as variations in STING expression within tumors. In this study, we present Mn-phenolic networks as a novel carrier for ADU-S100, a hydrophilic STING agonist, aimed at bolstering immunotherapy. These nanoparticles, termed TMA NMs, are synthesized through the coordination of tannic acid and manganese ions, with surface modification involving bovine serum albumin to enhance their colloidal stability. TMA NMs exhibit pH/GSH-responsive disintegration properties, enabling precise drug release. This effectively addresses drug stability issues and facilitates efficient intracellular drug delivery. Importantly, TMA NMs synergistically enhance the effects of ADU-S100 through the concurrent release of Mn2+, which serves as a sensitizer of the STING pathway, resulting in significant STING pathway activation. Upon systemic administration, these nanoparticles efficiently accumulate within tumors. The activation of STING pathways not only induces immunogenic cell death (ICD) in tumor cells but also orchestrates systemic remodeling of the immunosuppressive microenvironment. This includes the promotion of cytokine release, dendritic cell maturation, and T cell infiltration, leading to pronounced suppression of tumor growth. Combining with the excellent biocompatibility and biodegradability, this Mn-based nanocarrier represents a promising strategy for enhancing tumor immunotherapy through the cGAS-STING pathway. |
| first_indexed | 2024-04-24T23:24:00Z |
| format | Article |
| id | doaj.art-9b97bbdf52494735b887774a0f1c3500 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-24T23:24:00Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-9b97bbdf52494735b887774a0f1c35002024-03-16T05:09:03ZengElsevierMaterials Today Bio2590-00642024-06-0126101018Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapyYingcai Meng0Jiaxin Huang1Jinsong Ding2Haiyan Zhou3Yong Li4Wenhu Zhou5Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China; Xiangya Hospital, Central South University, Changsha 410008, Hunan, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, ChinaDepartment of Pathology, School of Basic Medicine, Central South University, China; Department of Pathology, Xiangya Hospital, Central South University, China; Corresponding author.Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China; Corresponding author.Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China; Corresponding author.The cGAS-STING pathway holds tremendous potential as a regulator of immune responses, offering a means to reshape the tumor microenvironment and enhance tumor immunotherapy. Despite the emergence of STING agonists, their clinical viability is hampered by stability and delivery challenges, as well as variations in STING expression within tumors. In this study, we present Mn-phenolic networks as a novel carrier for ADU-S100, a hydrophilic STING agonist, aimed at bolstering immunotherapy. These nanoparticles, termed TMA NMs, are synthesized through the coordination of tannic acid and manganese ions, with surface modification involving bovine serum albumin to enhance their colloidal stability. TMA NMs exhibit pH/GSH-responsive disintegration properties, enabling precise drug release. This effectively addresses drug stability issues and facilitates efficient intracellular drug delivery. Importantly, TMA NMs synergistically enhance the effects of ADU-S100 through the concurrent release of Mn2+, which serves as a sensitizer of the STING pathway, resulting in significant STING pathway activation. Upon systemic administration, these nanoparticles efficiently accumulate within tumors. The activation of STING pathways not only induces immunogenic cell death (ICD) in tumor cells but also orchestrates systemic remodeling of the immunosuppressive microenvironment. This includes the promotion of cytokine release, dendritic cell maturation, and T cell infiltration, leading to pronounced suppression of tumor growth. Combining with the excellent biocompatibility and biodegradability, this Mn-based nanocarrier represents a promising strategy for enhancing tumor immunotherapy through the cGAS-STING pathway.http://www.sciencedirect.com/science/article/pii/S2590006424000772STING pathwayDrug deliveryImmunomodulationTumor microenvironment |
| spellingShingle | Yingcai Meng Jiaxin Huang Jinsong Ding Haiyan Zhou Yong Li Wenhu Zhou Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy Materials Today Bio STING pathway Drug delivery Immunomodulation Tumor microenvironment |
| title | Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy |
| title_full | Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy |
| title_fullStr | Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy |
| title_full_unstemmed | Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy |
| title_short | Mn-phenolic networks as synergistic carrier for STING agonists in tumor immunotherapy |
| title_sort | mn phenolic networks as synergistic carrier for sting agonists in tumor immunotherapy |
| topic | STING pathway Drug delivery Immunomodulation Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424000772 |
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