Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux
The desirable curative effect in clinical immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metabolism in solid tumors. Although targeting metabolic reprogramming of tumor cells can restore the survival and function of immune cell...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10356/170559 |
| _version_ | 1811676219083587584 |
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| author | Yang, Chunzheng Wang, Man Chang, Mengyu Yuan, Meng Zhang, Wenying Tan, Jia Ding, Binbin Ma, Ping'an Lin, Jun |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Yang, Chunzheng Wang, Man Chang, Mengyu Yuan, Meng Zhang, Wenying Tan, Jia Ding, Binbin Ma, Ping'an Lin, Jun |
| author_sort | Yang, Chunzheng |
| collection | NTU |
| description | The desirable curative effect in clinical immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metabolism in solid tumors. Although targeting metabolic reprogramming of tumor cells can restore the survival and function of immune cells in the TME, it is also plagued by insufficient immunogenicity. Herein, an activatable immunomodulatory nanoadjuvant CuSe/CoSe2@syrosingopine (CSC@Syro) is constructed for simultaneously relieving immunosuppressive TME and boosting tumor immune response. Specifically, CuSe/CoSe2 (CSC) exhibits TME-activated glutathione (GSH) depletion and hydroxyl radical (•OH) generation for potential ferroptosis. Meanwhile, the remarkable photothermal conversion efficiency and elevated photocatalytic ROS level both promote CSC heterostructures to induce robust immunogenic cell death (ICD). Besides, the loaded syrosingopine inhibitor achieves LA metabolism blockade in cancer cells by downregulating the expression of monocarboxylate transporter 4 (MCT4), which could sensitize ferroptosis by intracellular milieu acidification and neutralize the acidic TME to alleviate immunosuppression. Hence, advanced metabolic modulation confers the potentiated immune infiltration of ICD-stimulated T lymphocytes and further reinforces antitumor therapy. In brief, CSC@Syro-mediated synergistic therapy could elicit potent immunogenicity and suppress tumor proliferation and metastasis effectually by integrating the tumor metabolic regulation and ferroptosis with immunotherapy. |
| first_indexed | 2024-10-01T02:17:59Z |
| format | Journal Article |
| id | ntu-10356/170559 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:17:59Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1705592023-09-19T05:30:37Z Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux Yang, Chunzheng Wang, Man Chang, Mengyu Yuan, Meng Zhang, Wenying Tan, Jia Ding, Binbin Ma, Ping'an Lin, Jun School of Chemistry, Chemical Engineering and Biotechnology Engineering::Bioengineering Biological Transport Ferroptosis The desirable curative effect in clinical immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metabolism in solid tumors. Although targeting metabolic reprogramming of tumor cells can restore the survival and function of immune cells in the TME, it is also plagued by insufficient immunogenicity. Herein, an activatable immunomodulatory nanoadjuvant CuSe/CoSe2@syrosingopine (CSC@Syro) is constructed for simultaneously relieving immunosuppressive TME and boosting tumor immune response. Specifically, CuSe/CoSe2 (CSC) exhibits TME-activated glutathione (GSH) depletion and hydroxyl radical (•OH) generation for potential ferroptosis. Meanwhile, the remarkable photothermal conversion efficiency and elevated photocatalytic ROS level both promote CSC heterostructures to induce robust immunogenic cell death (ICD). Besides, the loaded syrosingopine inhibitor achieves LA metabolism blockade in cancer cells by downregulating the expression of monocarboxylate transporter 4 (MCT4), which could sensitize ferroptosis by intracellular milieu acidification and neutralize the acidic TME to alleviate immunosuppression. Hence, advanced metabolic modulation confers the potentiated immune infiltration of ICD-stimulated T lymphocytes and further reinforces antitumor therapy. In brief, CSC@Syro-mediated synergistic therapy could elicit potent immunogenicity and suppress tumor proliferation and metastasis effectually by integrating the tumor metabolic regulation and ferroptosis with immunotherapy. This work is financially supported by the National Key Research and Development Program of China (2022YFB3804500), the National Natural Science Foundation of China (Grant Nos. NSFC 51929201, 51922097, 52102354, 52272282, and U22A20347), the Projects for Science and Technology Development Plan of Jilin Province (20220508089RC and 20210402046GH), the Postdoctoral Innovative Talents Support Program (BX2021360), and the project funded by the China Postdoctoral Science Foundation (2021M703130 and 2021M691919). 2023-09-19T05:30:37Z 2023-09-19T05:30:37Z 2023 Journal Article Yang, C., Wang, M., Chang, M., Yuan, M., Zhang, W., Tan, J., Ding, B., Ma, P. & Lin, J. (2023). Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux. Journal of the American Chemical Society, 145(13), 7205-7217. https://dx.doi.org/10.1021/jacs.2c12772 0002-7863 https://hdl.handle.net/10356/170559 10.1021/jacs.2c12772 36958054 2-s2.0-85151157676 13 145 7205 7217 en Journal of the American Chemical Society © 2023 American Chemical Society. All rights reserved. |
| spellingShingle | Engineering::Bioengineering Biological Transport Ferroptosis Yang, Chunzheng Wang, Man Chang, Mengyu Yuan, Meng Zhang, Wenying Tan, Jia Ding, Binbin Ma, Ping'an Lin, Jun Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title | Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title_full | Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title_fullStr | Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title_full_unstemmed | Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title_short | Heterostructural nanoadjuvant CuSe/CoSe₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| title_sort | heterostructural nanoadjuvant cuse cose₂ for potentiating ferroptosis and photoimmunotherapy through intratumoral blocked lactate efflux |
| topic | Engineering::Bioengineering Biological Transport Ferroptosis |
| url | https://hdl.handle.net/10356/170559 |
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