Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys
Despite the superior sensitivity of chemiluminescence over fluorescence, most chemiluminescence reporters only emit visible light, and have low water solubility, making them poorly equipped for in vivo imaging applications. Herein two near-infrared (NIR) chemiluminescent reporters (NCRs) with high r...
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sg-ntu-dr.10356-1544132021-12-22T06:06:50Z Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys Huang, Jingsheng Huang, Jiaguo Cheng, Penghui Jiang, Yuyan Pu, Kanyi School of Chemical and Biomedical Engineering Engineering::Chemical engineering Acute Kidney Injury Biosensors Despite the superior sensitivity of chemiluminescence over fluorescence, most chemiluminescence reporters only emit visible light, and have low water solubility, making them poorly equipped for in vivo imaging applications. Herein two near-infrared (NIR) chemiluminescent reporters (NCRs) with high renal clearance for real-time imaging of reactive oxygen and nitrogen species in the kidneys are synthesized. NCRs comprise a β-cyclodextrin unit and a modified dicyanomethylene-4H-pyran containing Schaap's dioxetane as the renal-clearance enabler and the chemiluminescent moiety, respectively. NCR1 and NCR2 specifically activate their NIR chemiluminescence towards superoxide anion (O2•−) and peroxynitrite (ONOO−), respectively. By virtue of their nanomolar sensitivity and high renal clearance, NCRs not only detect subtle upregulation of endogenous RONS in cells but also enable noninvasive monitoring of RONS in the kidneys under nephrotoxic exposure. The earlier activation of NCR1 relative to NCR2 implies the sequential upregulation of O2•− and ONOO− during drug-induced acute kidney injury (AKI). Moreover, detection of the fluorescence of excreted NCRs permits urinalysis of AKI, detecting the upregulation of RONS at least 24 h earlier than histological analysis. Thus, this study not only introduces ultrasensitive NIR chemiluminescent probes but also provides guidelines to transform them into legitimate imaging agents for organ-specific in vivo detection. Ministry of Education (MOE) Nanyang Technological University J.S.H. and J.G.H. contributed equally to this work. This work was supported by Nanyang Technological University (Start-up Grant: M4081627), and Singapore Ministry of Education Academic Research Fund Tier 1 (RG133/15 M4011559 and 2017-T1-002-134-RG147/17) and Tier 2 (MOE2016-T2-1-098). In vivo experiments were approved by the Institutional Animal Care and Use Committee (IACUC) for Animal Experiment, Singapore. 2021-12-22T06:06:49Z 2021-12-22T06:06:49Z 2020 Journal Article Huang, J., Huang, J., Cheng, P., Jiang, Y. & Pu, K. (2020). Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys. Advanced Functional Materials, 30(39), 2003628-. https://dx.doi.org/10.1002/adfm.202003628 1616-301X https://hdl.handle.net/10356/154413 10.1002/adfm.202003628 2-s2.0-85089311888 39 30 2003628 en M4081627 RG133/15 M4011559 017-T1-002-134-RG147/17 MOE2016-T2-1-09 Advanced Functional Materials © 2020 Wiley-VCH GmbH. All rights reserved. |
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Engineering::Chemical engineering Acute Kidney Injury Biosensors Huang, Jingsheng Huang, Jiaguo Cheng, Penghui Jiang, Yuyan Pu, Kanyi Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
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Despite the superior sensitivity of chemiluminescence over fluorescence, most chemiluminescence reporters only emit visible light, and have low water solubility, making them poorly equipped for in vivo imaging applications. Herein two near-infrared (NIR) chemiluminescent reporters (NCRs) with high renal clearance for real-time imaging of reactive oxygen and nitrogen species in the kidneys are synthesized. NCRs comprise a β-cyclodextrin unit and a modified dicyanomethylene-4H-pyran containing Schaap's dioxetane as the renal-clearance enabler and the chemiluminescent moiety, respectively. NCR1 and NCR2 specifically activate their NIR chemiluminescence towards superoxide anion (O2•−) and peroxynitrite (ONOO−), respectively. By virtue of their nanomolar sensitivity and high renal clearance, NCRs not only detect subtle upregulation of endogenous RONS in cells but also enable noninvasive monitoring of RONS in the kidneys under nephrotoxic exposure. The earlier activation of NCR1 relative to NCR2 implies the sequential upregulation of O2•− and ONOO− during drug-induced acute kidney injury (AKI). Moreover, detection of the fluorescence of excreted NCRs permits urinalysis of AKI, detecting the upregulation of RONS at least 24 h earlier than histological analysis. Thus, this study not only introduces ultrasensitive NIR chemiluminescent probes but also provides guidelines to transform them into legitimate imaging agents for organ-specific in vivo detection. |
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School of Chemical and Biomedical Engineering |
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School of Chemical and Biomedical Engineering Huang, Jingsheng Huang, Jiaguo Cheng, Penghui Jiang, Yuyan Pu, Kanyi |
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Article |
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Huang, Jingsheng Huang, Jiaguo Cheng, Penghui Jiang, Yuyan Pu, Kanyi |
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Huang, Jingsheng |
title |
Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
title_short |
Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
title_full |
Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
title_fullStr |
Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
title_full_unstemmed |
Near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
title_sort |
near-infrared chemiluminescent reporters for in vivo imaging of reactive oxygen and nitrogen species in kidneys |
publishDate |
2021 |
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https://hdl.handle.net/10356/154413 |
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1720447124573782016 |