A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy
NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1...
| প্রধান লেখক: | , , , , |
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| অন্যান্য লেখক: | |
| বিন্যাস: | Journal Article |
| ভাষা: | English |
| প্রকাশিত: |
2023
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| বিষয়গুলি: | |
| অনলাইন ব্যবহার করুন: | https://hdl.handle.net/10356/170296 |
| _version_ | 1826120675122741248 |
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| author | Cheng, Penghui He, Shasha Zhang, Chi Liu, Jing Pu, Kanyi |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Cheng, Penghui He, Shasha Zhang, Chi Liu, Jing Pu, Kanyi |
| author_sort | Cheng, Penghui |
| collection | NTU |
| description | NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1 (TNR1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker-specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem-locked design allows TNR1 to differentiate NETosis from neutrophil activation, while single-locked reporters fail to do so. The near-infrared signals from activated TNR1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near-infrared signals from activated TNR1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor-bearing living mice, but also proposes a generic approach for tandem-locked probe design. |
| first_indexed | 2024-10-01T05:20:20Z |
| format | Journal Article |
| id | ntu-10356/170296 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:20:20Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1702962023-09-06T02:30:20Z A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy Cheng, Penghui He, Shasha Zhang, Chi Liu, Jing Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Molecular Design Neutrophils NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1 (TNR1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker-specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem-locked design allows TNR1 to differentiate NETosis from neutrophil activation, while single-locked reporters fail to do so. The near-infrared signals from activated TNR1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near-infrared signals from activated TNR1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor-bearing living mice, but also proposes a generic approach for tandem-locked probe design. Ministry of Education (MOE) National Research Foundation (NRF) 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. 2023-09-06T02:30:20Z 2023-09-06T02:30:20Z 2023 Journal Article Cheng, P., He, S., Zhang, C., Liu, J. & Pu, K. (2023). A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy. Angewandte Chemie International Edition, 62(26), e202301625-. https://dx.doi.org/10.1002/anie.202301625 1433-7851 https://hdl.handle.net/10356/170296 10.1002/anie.202301625 37099322 2-s2.0-85159293496 26 62 e202301625 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-VCH GmbH. All rights reserved. |
| spellingShingle | Science::Medicine Molecular Design Neutrophils Cheng, Penghui He, Shasha Zhang, Chi Liu, Jing Pu, Kanyi A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title | A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title_full | A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title_fullStr | A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title_full_unstemmed | A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title_short | A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy |
| title_sort | tandem locked fluorescent netosis reporter for the prognosis assessment of cancer immunotherapy |
| topic | Science::Medicine Molecular Design Neutrophils |
| url | https://hdl.handle.net/10356/170296 |
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