Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes
Dual-locked activatable optical probes, leveraging the orthogonal effects of two biomarkers, hold great promise for the specific imaging of biological processes. However, their design approaches are limited to a short-distance energy or charge transfer mechanism, while the signal readout relies on f...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/179032 |
| _version_ | 1811680605565353984 |
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| author | Wei, Xin Xu, Cheng Cheng, Penghui Hu, Yuxuan Liu, Jing Xu, Mengke Huang, Jingsheng Zhang, Yan Pu, Kanyi |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Wei, Xin Xu, Cheng Cheng, Penghui Hu, Yuxuan Liu, Jing Xu, Mengke Huang, Jingsheng Zhang, Yan Pu, Kanyi |
| author_sort | Wei, Xin |
| collection | NTU |
| description | Dual-locked activatable optical probes, leveraging the orthogonal effects of two biomarkers, hold great promise for the specific imaging of biological processes. However, their design approaches are limited to a short-distance energy or charge transfer mechanism, while the signal readout relies on fluorescence, which inevitably suffers from tissue autofluorescence. Herein, we report a long-distance singlet oxygen transfer approach to develop a bienzyme-locked activatable afterglow probe (BAAP) that emits long-lasting self-luminescence without real-time light excitation for the dynamic imaging of an intratumoral granule enzyme. Composed of an immuno-biomarker-activatable singlet oxygen (1O2) donor and a cancer-biomarker-activatable 1O2 acceptor, BAAP is initially nonafterglow. Only in the presence of both immune and cancer biomarkers can 1O2 be generated by the activated donor and subsequently diffuse toward the activated acceptor, resulting in bright near-infrared afterglow with a high signal-to-background ratio and specificity toward an intratumoral granule enzyme. Thus, BAAP allows for real-time tracking of tumor-infiltrating cytotoxic T lymphocytes, enabling the evaluation of cancer immunotherapy and the differentiation of tumor from local inflammation with superb sensitivity and specificity, which are unachievable by single-locked probes. Thus, this study not only presents the first dual-locked afterglow probe but also proposes a new design way toward dual-locked probes via reactive oxygen species transfer processes. |
| first_indexed | 2024-10-01T03:27:43Z |
| format | Journal Article |
| id | ntu-10356/179032 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:27:43Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1790322024-07-19T15:31:41Z Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes Wei, Xin Xu, Cheng Cheng, Penghui Hu, Yuxuan Liu, Jing Xu, Mengke Huang, Jingsheng Zhang, Yan Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Bienzymes Biological marker Dual-locked activatable optical probes, leveraging the orthogonal effects of two biomarkers, hold great promise for the specific imaging of biological processes. However, their design approaches are limited to a short-distance energy or charge transfer mechanism, while the signal readout relies on fluorescence, which inevitably suffers from tissue autofluorescence. Herein, we report a long-distance singlet oxygen transfer approach to develop a bienzyme-locked activatable afterglow probe (BAAP) that emits long-lasting self-luminescence without real-time light excitation for the dynamic imaging of an intratumoral granule enzyme. Composed of an immuno-biomarker-activatable singlet oxygen (1O2) donor and a cancer-biomarker-activatable 1O2 acceptor, BAAP is initially nonafterglow. Only in the presence of both immune and cancer biomarkers can 1O2 be generated by the activated donor and subsequently diffuse toward the activated acceptor, resulting in bright near-infrared afterglow with a high signal-to-background ratio and specificity toward an intratumoral granule enzyme. Thus, BAAP allows for real-time tracking of tumor-infiltrating cytotoxic T lymphocytes, enabling the evaluation of cancer immunotherapy and the differentiation of tumor from local inflammation with superb sensitivity and specificity, which are unachievable by single-locked probes. Thus, this study not only presents the first dual-locked afterglow probe but also proposes a new design way toward dual-locked probes via reactive oxygen species transfer processes. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version Y.Z. thanks the National Natural Science Foundation of China (22322406) for financial support. K.P. thanks the Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005) and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE-T2EP30220-0010 and MOE-T2EP30221-0004) for financial support. 2024-07-16T07:47:25Z 2024-07-16T07:47:25Z 2024 Journal Article Wei, X., Xu, C., Cheng, P., Hu, Y., Liu, J., Xu, M., Huang, J., Zhang, Y. & Pu, K. (2024). Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes. Journal of the American Chemical Society, 146(25), 17393-17403. https://dx.doi.org/10.1021/jacs.4c05012 0002-7863 https://hdl.handle.net/10356/179032 10.1021/jacs.4c05012 38860693 2-s2.0-85196027352 25 146 17393 17403 en NRF-NRFI07-2021-0005 MOE-T2EP30220-0010 MOE-T2EP30221-0004 Journal of the American Chemical Society © 2024 American Chemical Society. 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/10.1021/jacs.4c05012. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Bienzymes Biological marker Wei, Xin Xu, Cheng Cheng, Penghui Hu, Yuxuan Liu, Jing Xu, Mengke Huang, Jingsheng Zhang, Yan Pu, Kanyi Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title | Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title_full | Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title_fullStr | Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title_full_unstemmed | Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title_short | Leveraging long-distance singlet-oxygen transfer for bienzyme-locked afterglow imaging of intratumoral granule enzymes |
| title_sort | leveraging long distance singlet oxygen transfer for bienzyme locked afterglow imaging of intratumoral granule enzymes |
| topic | Medicine, Health and Life Sciences Bienzymes Biological marker |
| url | https://hdl.handle.net/10356/179032 |
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