Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion
The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exoso...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221138352500125X |
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| author | Zheng Wang Ronghui Yin Lin Zhang Shiyu Li Zhanwei Zhou Minjie Sun |
| author_facet | Zheng Wang Ronghui Yin Lin Zhang Shiyu Li Zhanwei Zhou Minjie Sun |
| author_sort | Zheng Wang |
| collection | DOAJ |
| description | The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer. |
| format | Article |
| id | doaj-art-acbc1f83d11d48d3a2f72ca2f67c9c6d |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-acbc1f83d11d48d3a2f72ca2f67c9c6d2025-08-20T03:49:45ZengElsevierActa Pharmaceutica Sinica B2211-38352025-05-011552673268610.1016/j.apsb.2025.03.007Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretionZheng Wang0Ronghui Yin1Lin Zhang2Shiyu Li3Zhanwei Zhou4Minjie Sun5NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaNMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaNMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaNMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaCorresponding authors.; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaCorresponding authors.; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaThe αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.http://www.sciencedirect.com/science/article/pii/S221138352500125XCarrier free nanomedicineExosomes depletionImmunogenic cell deathChemo-immunotherapyGSH responsive delivery systemProgrammed death ligand 1 |
| spellingShingle | Zheng Wang Ronghui Yin Lin Zhang Shiyu Li Zhanwei Zhou Minjie Sun Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion Acta Pharmaceutica Sinica B Carrier free nanomedicine Exosomes depletion Immunogenic cell death Chemo-immunotherapy GSH responsive delivery system Programmed death ligand 1 |
| title | Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion |
| title_full | Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion |
| title_fullStr | Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion |
| title_full_unstemmed | Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion |
| title_short | Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion |
| title_sort | sulfafurazole dimers potentiate chemo immunotherapy of low immunogenic breast cancer by preventing the pd l1 exosomes secretion |
| topic | Carrier free nanomedicine Exosomes depletion Immunogenic cell death Chemo-immunotherapy GSH responsive delivery system Programmed death ligand 1 |
| url | http://www.sciencedirect.com/science/article/pii/S221138352500125X |
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