Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization
The low immunogenicity of tumors, coupled with abnormal and dysfunctional tumor vasculature, hinders the infiltration and function of effector T cells and suppresses the efficacy of immunotherapy. Herein, we developed a defective-copper-based metal-organic framework single-site nanozyme (F@D-CHTP SN...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/181694 |
| _version_ | 1826128130146828288 |
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| author | Liu, Yang Zhao, Huan Niu, Rui Zhang, Bin Lim, Garrick Boon Teck Song, Shuyan Wang, Yinghui Zhang, Hongjie Zhao, Yanli |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Liu, Yang Zhao, Huan Niu, Rui Zhang, Bin Lim, Garrick Boon Teck Song, Shuyan Wang, Yinghui Zhang, Hongjie Zhao, Yanli |
| author_sort | Liu, Yang |
| collection | NTU |
| description | The low immunogenicity of tumors, coupled with abnormal and dysfunctional tumor vasculature, hinders the infiltration and function of effector T cells and suppresses the efficacy of immunotherapy. Herein, we developed a defective-copper-based metal-organic framework single-site nanozyme (F@D-CHTP SN) with co-loaded MSA-2 (stimulator of interferon genes [STING] agonist) and fruquintinib (vascular endothelial growth factor receptor [VEGFR] inhibitor). The conjugated organic ligands and highly exposed unsaturated Cu-O2 single-atom sites endow F@D-CHTP SN with excellent reactive oxygen species generation activity, which can disrupt the cellular redox balance, impair mitochondrial function, and ultimately induce cuproptosis and ferroptosis, enhancing tumor immunogenicity. Meanwhile, intratumoral STING activation and VEGFR blockade synergistically promote tumor vasculature normalization, further reshaping the immunosuppressive microenvironment and enhancing T cell infiltration to achieve effective tumor suppression. Our work demonstrates the feasibility and significant synergistic effects of initiating cascade-enhancing immunity by combining cuproptosis and ferroptosis with STING activation and tumor vasculature normalization. |
| first_indexed | 2025-03-09T14:44:56Z |
| format | Journal Article |
| id | ntu-10356/181694 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-03-09T14:44:56Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1816942024-12-20T15:32:18Z Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization Liu, Yang Zhao, Huan Niu, Rui Zhang, Bin Lim, Garrick Boon Teck Song, Shuyan Wang, Yinghui Zhang, Hongjie Zhao, Yanli School of Chemistry, Chemical Engineering and Biotechnology Chemistry Cuproptosis Defective engineering The low immunogenicity of tumors, coupled with abnormal and dysfunctional tumor vasculature, hinders the infiltration and function of effector T cells and suppresses the efficacy of immunotherapy. Herein, we developed a defective-copper-based metal-organic framework single-site nanozyme (F@D-CHTP SN) with co-loaded MSA-2 (stimulator of interferon genes [STING] agonist) and fruquintinib (vascular endothelial growth factor receptor [VEGFR] inhibitor). The conjugated organic ligands and highly exposed unsaturated Cu-O2 single-atom sites endow F@D-CHTP SN with excellent reactive oxygen species generation activity, which can disrupt the cellular redox balance, impair mitochondrial function, and ultimately induce cuproptosis and ferroptosis, enhancing tumor immunogenicity. Meanwhile, intratumoral STING activation and VEGFR blockade synergistically promote tumor vasculature normalization, further reshaping the immunosuppressive microenvironment and enhancing T cell infiltration to achieve effective tumor suppression. Our work demonstrates the feasibility and significant synergistic effects of initiating cascade-enhancing immunity by combining cuproptosis and ferroptosis with STING activation and tumor vasculature normalization. National Research Foundation (NRF) Submitted/Accepted version This work was supported by the National Research Foundation Singapore under its Competitive Research Programme (NRF-CRP26-2021-0002), the National Natural Science Foundation of China (52022094), and the Basic Science Center Project of the National Natural Science Foundation of China (22388101). 2024-12-18T07:49:45Z 2024-12-18T07:49:45Z 2024 Journal Article Liu, Y., Zhao, H., Niu, R., Zhang, B., Lim, G. B. T., Song, S., Wang, Y., Zhang, H. & Zhao, Y. (2024). Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization. Chem. https://dx.doi.org/10.1016/j.chempr.2024.08.020 2451-9308 https://hdl.handle.net/10356/181694 10.1016/j.chempr.2024.08.020 en NRF-CRP26-2021-0002 Chem © 2024 Elsevier Inc. 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/10.1016/j.chempr.2024.08.020. application/pdf |
| spellingShingle | Chemistry Cuproptosis Defective engineering Liu, Yang Zhao, Huan Niu, Rui Zhang, Bin Lim, Garrick Boon Teck Song, Shuyan Wang, Yinghui Zhang, Hongjie Zhao, Yanli Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title | Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title_full | Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title_fullStr | Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title_full_unstemmed | Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title_short | Single-site nanozyme with exposed unsaturated Cu-O2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| title_sort | single site nanozyme with exposed unsaturated cu o2 sites for tumor therapy by coordinating innate immunity and vasculature normalization |
| topic | Chemistry Cuproptosis Defective engineering |
| url | https://hdl.handle.net/10356/181694 |
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