A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization
Tumor-associated macrophages (TAMs) play a role in both pro- and anti-tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from...
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sg-ntu-dr.10356-1788942024-07-12T15:31:51Z A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization Huang, Jingsheng Xu, Mengke Cheng, Penghui Yu, Jie Wu, Jiayan Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Chemistry Infrared devices Tumors Tumor-associated macrophages (TAMs) play a role in both pro- and anti-tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem-locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron-withdrawing groups, near-infrared (NIR) chemiluminophores are screened out to possess record-long emission (over 800 nm), record-high CL quantum yield (2.7 % einstein/mol), and prolonged half-life (7.7 h). Based on an ideal chemiluminophore, the tandem-locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ-glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem-lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem-locked CL probes for enhanced imaging specificity. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version K.P. thanks Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support. 2024-07-10T02:41:24Z 2024-07-10T02:41:24Z 2024 Journal Article Huang, J., Xu, M., Cheng, P., Yu, J., Wu, J. & Pu, K. (2024). A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization. Angewandte Chemie, 63(21), e202319780-. https://dx.doi.org/10.1002/anie.202319780 0044-8249 https://hdl.handle.net/10356/178894 10.1002/anie.202319780 38523406 2-s2.0-85190449412 21 63 e202319780 en NRF‐NRFI07‐2021‐0005 MOE‐T2EP30220‐0010 MOE‐T2EP30221‐0004 Angewandte Chemie © 2024 Wiley-VCH GmbH. 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://dx.doi.org/10.1002/anie.202319780. application/pdf |
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Chemistry Infrared devices Tumors Huang, Jingsheng Xu, Mengke Cheng, Penghui Yu, Jie Wu, Jiayan Pu, Kanyi A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
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Tumor-associated macrophages (TAMs) play a role in both pro- and anti-tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem-locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron-withdrawing groups, near-infrared (NIR) chemiluminophores are screened out to possess record-long emission (over 800 nm), record-high CL quantum yield (2.7 % einstein/mol), and prolonged half-life (7.7 h). Based on an ideal chemiluminophore, the tandem-locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ-glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem-lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem-locked CL probes for enhanced imaging specificity. |
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School of Chemistry, Chemical Engineering and Biotechnology |
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School of Chemistry, Chemical Engineering and Biotechnology Huang, Jingsheng Xu, Mengke Cheng, Penghui Yu, Jie Wu, Jiayan Pu, Kanyi |
format |
Article |
author |
Huang, Jingsheng Xu, Mengke Cheng, Penghui Yu, Jie Wu, Jiayan Pu, Kanyi |
author_sort |
Huang, Jingsheng |
title |
A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
title_short |
A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
title_full |
A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
title_fullStr |
A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
title_full_unstemmed |
A tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
title_sort |
tandem-locked chemiluminescent probe for imaging of tumor-associated macrophage polarization |
publishDate |
2024 |
url |
https://hdl.handle.net/10356/178894 |
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1814047445715255296 |