Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy
The efficacy of combination immunotherapy has been limited by tumor specificity and immune-related adverse events (irAEs). Herein, we report the development of polymeric STING pro-agonists (PSPA), whose sono-immunotherapeutic efficacy is activated by sono-irradiation and elevated glutathione (GSH) w...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/171012 |
| _version_ | 1826125481397714944 |
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| author | Yu, Jie He, Shasha Zhang, Chi Xu, Cheng Huang, Jingsheng Xu, Mengke Pu, Kanyi |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Yu, Jie He, Shasha Zhang, Chi Xu, Cheng Huang, Jingsheng Xu, Mengke Pu, Kanyi |
| author_sort | Yu, Jie |
| collection | NTU |
| description | The efficacy of combination immunotherapy has been limited by tumor specificity and immune-related adverse events (irAEs). Herein, we report the development of polymeric STING pro-agonists (PSPA), whose sono-immunotherapeutic efficacy is activated by sono-irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA-2) via the GSH-activatable linkers. Under sono-irradiation, PSPA serves as a sonosensitizer to generate 1 O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA-2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off-target side effects. The activation of the STING pathway elevates the interferon-β level and synergizes with SDT to enhance the anti-tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono-immunotherapy. |
| first_indexed | 2024-10-01T06:37:00Z |
| format | Journal Article |
| id | ntu-10356/171012 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:37:00Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1710122023-10-15T15:38:31Z Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy Yu, Jie He, Shasha Zhang, Chi Xu, Cheng Huang, Jingsheng Xu, Mengke Pu, Kanyi Lee Kong Chian School of Medicine (LKCMedicine) School of Chemistry, Chemical Engineering and Biotechnology Science::Medicine Cancer Therapy Immunotherapy The efficacy of combination immunotherapy has been limited by tumor specificity and immune-related adverse events (irAEs). Herein, we report the development of polymeric STING pro-agonists (PSPA), whose sono-immunotherapeutic efficacy is activated by sono-irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA-2) via the GSH-activatable linkers. Under sono-irradiation, PSPA serves as a sonosensitizer to generate 1 O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA-2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off-target side effects. The activation of the STING pathway elevates the interferon-β level and synergizes with SDT to enhance the anti-tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono-immunotherapy. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version K. P. thanks Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support. 2023-10-10T05:01:20Z 2023-10-10T05:01:20Z 2023 Journal Article Yu, J., He, S., Zhang, C., Xu, C., Huang, J., Xu, M. & Pu, K. (2023). Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy. Angewandte Chemie International Edition, 62(32), e202307272-. https://dx.doi.org/10.1002/anie.202307272 1433-7851 https://hdl.handle.net/10356/171012 10.1002/anie.202307272 37312610 2-s2.0-85163580162 32 62 e202307272 en NRF-NRFI07-2021-0005 2019-T1-002-045 RG125/19 RT05/20 MOE-T2EP30220-0010 MOE-T2EP30221-0004 Angewandte Chemie International Edition © 2023 Wiley-VCHGmbH. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1002/anie.202307272. application/pdf |
| spellingShingle | Science::Medicine Cancer Therapy Immunotherapy Yu, Jie He, Shasha Zhang, Chi Xu, Cheng Huang, Jingsheng Xu, Mengke Pu, Kanyi Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title | Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title_full | Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title_fullStr | Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title_full_unstemmed | Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title_short | Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy |
| title_sort | polymeric sting pro agonists for tumor specific sonodynamic immunotherapy |
| topic | Science::Medicine Cancer Therapy Immunotherapy |
| url | https://hdl.handle.net/10356/171012 |
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