Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine
Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging a...
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sg-ntu-dr.10356-1690672023-06-28T01:46:31Z Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine He, Shasha Cheng, Penghui Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Engineering::Chemical engineering Cancer Immunotherapy Current Imaging Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging agents do not distinguish TILs from leukocytes resident in other tissues. Here we report a library of activatable molecular probes for the imaging, via near-infrared fluorescence, of specific TILs (including M1 macrophages, cytotoxic T lymphocytes and neutrophils) in vivo in real time and also via excreted urine, owing to the probes' renal clearance. The fluorescence of the probes is activated only in the presence of both tumour and leukocyte biomarkers, which allows for the imaging of populations of specific TILs in mouse models of cancers with sensitivities and specificities similar to those achieved via flow-cytometric analyses of biopsied tumour tissues. We also show that the probes enable the non-invasive evaluation of the immunogenicity of different tumours, the dynamic monitoring of responses to immunotherapies and the accurate prediction of tumour growth under various treatments. Ministry of Education (MOE) National Research Foundation (NRF) K.P. thanks the Singapore Ministry of Education, Academic Research Fund Tier 1 (RG125/19; RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010) and the Singapore National Research Foundation (NRF-NRFI07-2021-0005) for financial support. 2023-06-28T01:46:31Z 2023-06-28T01:46:31Z 2023 Journal Article He, S., Cheng, P. & Pu, K. (2023). Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine. Nature Biomedical Engineering, 7(3), 281-297. https://dx.doi.org/10.1038/s41551-023-01009-1 2157-846X https://hdl.handle.net/10356/169067 10.1038/s41551-023-01009-1 36941352 2-s2.0-85150457130 3 7 281 297 en RG125/19 RT05/20 MOE2018-T2-2-042 MOE-T2EP30220-0010 NRF-NRFI07-2021-0005 Nature Biomedical Engineering © 2023 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved. |
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Engineering::Chemical engineering Cancer Immunotherapy Current Imaging He, Shasha Cheng, Penghui Pu, Kanyi Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
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Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging agents do not distinguish TILs from leukocytes resident in other tissues. Here we report a library of activatable molecular probes for the imaging, via near-infrared fluorescence, of specific TILs (including M1 macrophages, cytotoxic T lymphocytes and neutrophils) in vivo in real time and also via excreted urine, owing to the probes' renal clearance. The fluorescence of the probes is activated only in the presence of both tumour and leukocyte biomarkers, which allows for the imaging of populations of specific TILs in mouse models of cancers with sensitivities and specificities similar to those achieved via flow-cytometric analyses of biopsied tumour tissues. We also show that the probes enable the non-invasive evaluation of the immunogenicity of different tumours, the dynamic monitoring of responses to immunotherapies and the accurate prediction of tumour growth under various treatments. |
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School of Chemistry, Chemical Engineering and Biotechnology |
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School of Chemistry, Chemical Engineering and Biotechnology He, Shasha Cheng, Penghui Pu, Kanyi |
format |
Article |
author |
He, Shasha Cheng, Penghui Pu, Kanyi |
author_sort |
He, Shasha |
title |
Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
title_short |
Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
title_full |
Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
title_fullStr |
Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
title_full_unstemmed |
Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
title_sort |
activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine |
publishDate |
2023 |
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https://hdl.handle.net/10356/169067 |
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1772825419179884544 |