Activatable NIR-II Fluorescence Probe for Highly Sensitive and Selective Visualization of Glutathione In Vivo
Abstract
Visualization of glutathione (GSH) enables us to understand GSH-related pathophysiological processes in living subjects. Currently, in vivo visualization methods of GSH are based on visible or first near-infrared (NIR-I) window fluorescence (FL) probes, which possess limitations due to their low tissue penetration depth and strong tissue autofluorescence. Herein, we developed a GSH-activatable second near-infrared (NIR-II) window FL probe (denoted as LET-7) for highly sensitive and selective visualization of GSH in vivo . LET-7, composed of an anionic polymethylcyanide skeleton linked with a FL quenching group of 3,5-bis(trifluoromethyl)benzenethiol, can be specifically activated by GSH, thus triggering a significant NIR-II FL emission enhancement with excellent photostability, which enables us to efficiently distinguish GSH from closely related low-molecular-weight biothiols. The limit of detection of LET-7 for GSH was determined to be as low as 85 nM. Most intriguingly, the in vivo studies demonstrated that LET-7 showed high sensitivity and good selectivity toward GSH. Therefore, our study provides a solution to design activatable NIR-II FL probes for in vivo imaging of GSH and other disease-related biomarkers.
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Lin et al. pioneered the development of a GSH-activatable NIR-II probe (LET-7), enabling highly sensitive and selective visualization of GSH in vivo.
“Lin et al. pioneered the development of a GSH-activatable NIR-II probe (LET-7), enabling highly sensitive and selective visualization of GSH in vivo (Fig. 19a)220.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [220]
Upon exposure to GSH, LET-7 exhibited a significant fluorescence enhancement at 928 nm, achieving a remarkably low detection limit of 85 nM.
“Upon exposure to GSH, LET-7 exhibited a significant fluorescence enhancement at 928 nm, achieving a remarkably low detection limit of 85 nM.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [220]
Cites
Glutathione Metabolism and Its Implications for Health
Wu, G., Lupton, J. R., Turner, N. D., Fang, Y.-Z., & Yang, S. (2004) · The Journal of Nutrition · doi:10.1093/jn/134.3.489 · Cited by 3,842 · see citing works
Near-infrared fluorophores for biomedical imaging
Hong, G., Antaris, A. L., & Dai, H. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-016-0010 · Cited by 3,013 · see citing works
Second window for in vivo imaging
Smith, A. M., Mancini, M. C., & Nie, S. (2009) · Nature Nanotechnology · doi:10.1038/nnano.2009.326 · Cited by 2,848 · see citing works
Selective Modification of Glutathione Metabolism
Meister, A. (1983) · Science · doi:10.1126/science.6836290 · Cited by 1,267 · see citing works
Glutathione metabolism in cancer progression and treatment resistance
Bansal, A., & Simon, M. C. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201804161 · Cited by 1,234 · see citing works
Advanced Fluorescence Imaging Technology in the Near-Infrared-II Window for Biomedical Applications
Li, C., Chen, G., Zhang, Y., Wu, F., & Wang, Q. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c07022 · Cited by 1,037 · see citing works
Niu, L., Guan, Y., Chen, Y., Wu, L., Tung, C., & Yang, Q. (2012) · Journal of the American Chemical Society · doi:10.1021/ja309079f · Cited by 903 · see citing works
Yin, J., Kwon, Y., Kim, D., Lee, D.-Y., Kim, G., Hu, Y., Ryu, J.-H., & Yoon, J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja412628z · Cited by 596 · see citing works
Simultaneous Fluorescence Sensing of Cys and GSH from Different Emission Channels
Liu, J., Sun, Y., Huo, Y., Zhang, H., Wang, L., Zhang, P., Song, D., Shi, Y., & Guo, W. (2013) · Journal of the American Chemical Society · doi:10.1021/ja409578w · Cited by 586 · see citing works
Umezawa, K., Yoshida, M., Kamiya, M., Yamasoba, T., & Urano, Y. (2016) · Nature Chemistry · doi:10.1038/nchem.2648 · Cited by 504 · see citing works
Glutathione metabolism and its role in hepatotoxicity
DeLeve, L. D., & Kaplowitz, N. (1991) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(91)90029-l · Cited by 495 · see citing works
Fluorescent Probes with Multiple Binding Sites for the Discrimination of Cys, Hcy, and GSH
Yin, C., Xiong, K., Huo, F., Salamanca, J. C., & Strongin, R. M. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201704084 · Cited by 493 · see citing works
Lim, S.-Y., Hong, K.-H., Kim, D. I., Kwon, H., & Kim, H.-J. (2014) · Journal of the American Chemical Society · doi:10.1021/ja500962u · Cited by 462 · see citing works
Glutathione metabolism and Parkinson's disease
Smeyne, M., & Smeyne, R. J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.001 · Cited by 436 · see citing works
Meister, A. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)51106-7 · Cited by 429 · see citing works
A Reversible Fluorescent Probe for Real‐Time Quantitative Monitoring of Cellular Glutathione
Liu, Z., Zhou, X. M., Yu, M., Hu, Y., Kwon, N., Wu, X. F., & Yoon, J. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201702114 · Cited by 313 · see citing works
Yin, G., Niu, T., Gan, Y., Yu, T. Y., Yin, P., Chen, H., Zhang, Y., Li, H., & Yao, S. Z. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201800485 · Cited by 312 · see citing works
Wang, F., Zhou, L., Zhao, C., Wang, R., Fei, Q., Luo, S., Guo, Z., Tian, H., & Zhu, W. (2015) · Chemical Science · doi:10.1039/c5sc00216h · Cited by 274 · see citing works
Inoue, T., & Kirchhoff, J. R. (2002) · Analytical Chemistry · doi:10.1021/ac0108515 · Cited by 245 · see citing works
Changes in Hepatic Glutathione Metabolism in Diabetes
McLennan, S. V., Heffernan, S. J., Wright, L., Rae, C. D., Fisher, E., Yue, D. K., & Turtle, J. R. (1991) · Diabetes · doi:10.2337/diab.40.3.344 · Cited by 219 · see citing works
Xu, Z., Huang, X., Han, X., Wu, D., Zhang, B., Tan, Y. C., Cao, M., Liu, S. H., Yin, J., & Yoon, J. (2018) · Chem · doi:10.1016/j.chempr.2018.04.003 · Cited by 195 · see citing works
Xiong, K., Huo, F., Chao, J., Zhang, Y., & Yin, C. (2018) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04485 · Cited by 176 · see citing works
Yan, H., Huo, F., Yue, Y., Chao, J., & Yin, C. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c10840 · Cited by 158 · see citing works
Lee, D., Kim, G., Yin, J., & Yoon, J. (2015) · Chemical Communications · doi:10.1039/c5cc01071c · Cited by 153 · see citing works
Xie, J., Li, C., Li, Y., Fei, J., Xu, F., Ouyang, J., & Liu, J. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b02646 · Cited by 153 · see citing works
Kaczyńska, A., Pelsers, M. M. A. L., Bochowicz, A., Kostrubiec, M., Glatz, J. F. C., & Pruszczyk, P. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2006.02.032 · Cited by 129 · see citing works
Chen, X., Niu, L., Shao, N., & Yang, Q. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b00169 · Cited by 109 · see citing works
Glutathione metabolism in sepsis
Biolo, G., Antonione, R., & Cicco, M. D. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000278913.19123.13 · Cited by 105 · see citing works
Yin, J., Kwon, Y., Kim, D., Lee, D., Kim, G., Hu, Y., Ryu, J.-H., & Yoon, J. (2015) · Nature Protocols · doi:10.1038/nprot.2015.109 · Cited by 104 · see citing works
Vacek, J., Klejdus, B., Petrlová, J., Lojková, L., & Kubáň, V. (2006) · The Analyst · doi:10.1039/b606432a · Cited by 94 · see citing works
Gao, X., Ma, G., Jiang, C., Zeng, L., Jiang, S., Huang, P., & Lin, J. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b00109 · Cited by 76 · see citing works
Self-citationIn Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects
Zeng, L., Ma, G., Xu, H., Mu, J., Li, F., Gao, X., Deng, Z., Qu, J., Huang, P., & Lin, J. (2019) · Small · doi:10.1002/smll.201803866 · Cited by 56 · see citing works
Self-citationTian, M., Liu, Y., & Jiang, F. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c03418 · Cited by 52 · see citing works
Neuroprotective Roles of the Reverse Transsulfuration Pathway in Alzheimer’s Disease
Paul, B. D. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.659402 · Cited by 42 · see citing works
Efficient light harvesting anionic heptamethine cyanine–[60] and [70]fullerene hybrids
Villegas, C., Krokos, E., Bouit, P., de la Cruz, J. L. D., Guldi, D. M., & Martı́n, N. (2011) · Energy & Environmental Science · doi:10.1039/c0ee00497a · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Near-infrared (NIR) fluorescence-emitting small organic molecules for cancer imaging and therapy
Li, H., Kim, Y., Jung, H., Hyun, J. Y., & Shin, I. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00722c · Cited by 356 · see citing works
Activatable NIR-II organic fluorescent probes for bioimaging
Zhang, X., Li, S., Ma, H., Wang, H., Zhang, X., & Zhang, X. (2022) · Theranostics · doi:10.7150/thno.71359 · Cited by 138 · see citing works
Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo
Fu, Q., Yang, X. P., Wang, M., Zhu, K., Wang, Y., & Song, J. (2024) · ACS Nano · doi:10.1021/acsnano.3c10659 · Cited by 97 · see citing works
Cellular Redox Regulation and Fluorescence Imaging
Li, Y., Liu, G., Cheng, S., Zhang, J., Yao, X., Xie, X., Xu, C., Tang, Y., Wang, X., & Tang, B. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00080 · Cited by 82 · see citing works
Self-citationDong, H. Y., Chen, W., Xu, K., Zheng, L., Wei, B., Liu, R., Yang, J., Wang, T., Zhou, Y., Zhang, Y., et al. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.4c05627 · Cited by 67 · see citing works
Near-Infrared Probes for Biothiols (Cysteine, Homocysteine, and Glutathione): A Comprehensive Review
Kaushik, R., Nehra, N., Novakova, V., & Zimčík, P. (2022) · ACS Omega · doi:10.1021/acsomega.2c06218 · Cited by 53 · see citing works
Nagendraraj, T., Priya, S. V., Annaraj, J., & Sagadevan, S. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215368 · Cited by 52 · see citing works
Zhao, Y., Li, L., Ye, Q., Gong, Y., Yang, R., & Liu, H. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c02664 · Cited by 47 · see citing works
Development of Polymethine Dyes for NIR‐II Fluorescence Imaging and Therapy
Chen, X., Li, J., Roy, S., Ullah, Z., Gu, J., Huang, H., Yu, C., Wang, X., Wang, H., Zhang, Y., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202304506 · Cited by 48 · see citing works
Design strategies and applications of smart optical probes in the second near-infrared window
Chang, B., Chen, J., Bao, J., Dong, K., Chen, S., & Cheng, Z. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114637 · Cited by 43 · see citing works
Wang, M., Bai, S., & Zhang, Y. (2025) · Chemical Society Reviews · doi:10.1039/d5cs00502g · Cited by 41 · see citing works
Bioresponsive fluorescent probes active in the second near‐infrared window
Chen, Y., Chen, J., & Chang, B. (2023) · iRadiology · doi:10.1002/ird3.10 · Cited by 31 · see citing works
Liu, N., He, S., Cheng, Z., & Hu, J. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.216511 · Cited by 30 · see citing works
Luo, C., Chen, Y., Gu, J., Cai, H., Lin, H., Jin, Z., & Huang, C. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c01309 · Cited by 26 · see citing works
Activatable Molecular Probes With Clinical Promise for NIR‐II Fluorescent Imaging
Chen, Z., Zhou, Y., Li, L., Ma, W., Li, Y., & Yang, Z. (2025) · Small · doi:10.1002/smll.202411787 · Cited by 26 · see citing works
A glutathione-activated NIR-II fluorescent probe for precise localization of micrometastases
Huang, Y. D., Tian, F., Sun, L., Ji, C., Grimes, C. A., & Cai, Q. (2023) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2023.133457 · Cited by 22 · see citing works
Ding, G., Wang, X., Derong, L., Meng, S., Zhou, L., Fan, Y., Ling-hu, C., Meng, J. P., Si, W., Chen, Q., et al. (2022) · Dyes and Pigments · doi:10.1016/j.dyepig.2022.110762 · Cited by 21 · see citing works
Lei, S., Jiang, K., Zhang, C., Sun, W., Pan, Y., Wang, D., Huang, P., & Lin, J. (2023) · Research · doi:10.34133/research.0286 · Cited by 19 · see citing works
Self-citationMeng, X., Song, J., Du, Z., Tao, Y., & Qi, J. (2025) · ACS Nano · doi:10.1021/acsnano.5c07280 · Cited by 18 · see citing works
Polymeric agents for activatable fluorescence, self-luminescence and photoacoustic imaging
Zhu, J., Zhu, R., & Miao, Q. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114330 · Cited by 18 · see citing works
High-precision detection and navigation surgery of colorectal cancer micrometastases
Ma, S., Sun, B., Li, M., Han, T., Yu, C., Wang, X., Zheng, X., Li, S., Zhu, S., & Wang, Q. (2023) · Journal of Nanobiotechnology · doi:10.1186/s12951-023-02171-z · Cited by 19 · see citing works
Chi, Y., Hu, Q., Yi, S., Qu, H., & Xiao, Y. C. (2023) · Talanta · doi:10.1016/j.talanta.2023.124668 · Cited by 17 · see citing works
Organic small-molecule NIR-II fluorophores for tumor phototheranostics
Xiang, D., Wang, Z., Zheng, H., Tang, Y., & Li, Q. (2026) · Light: Science & Applications · doi:10.1038/s41377-026-02212-w · Cited by 22 · see citing works
“19a) 220 .”
Wang, Y., Zhao, G., Liu, Y., Wang, R., Xing, Y., Dou, K., & Yu, F. (2025) · Sensors and Actuators B: Chemical · doi:10.1016/j.snb.2024.137005 · Cited by 16 · see citing works
Wang, J., Yin, C., & Huo, F. (2024) · The Analyst · doi:10.1039/d4an01373e · Cited by 15 · see citing works
Zhang, K., Zhang, Y., Lan, Y., Wang, F., Gou, Z., Yan, M., & Zuo, Y. (2023) · Analytica Chimica Acta · doi:10.1016/j.aca.2023.340939 · Cited by 15 · see citing works
Liu, C., Rong, X., Li, X., Gao, N., Qu, L., Peng, Y., Shi, J., Yu, M., Sheng, W., & Zhu, B. (2023) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2023.133841 · Cited by 14 · see citing works
Advanced second near-infrared fluorophores for bioapplications
Bai, Q., Yang, Q., Liu, Y., Li, A., Yin, X.-B., & Wu, S. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.217146 · Cited by 14 · see citing works
Fu, D., Wang, Y., Kaiwen, L., Huang, L., Xu, J., & Wu, H. (2023) · RSC Advances · doi:10.1039/d3ra04074g · Cited by 13 · see citing works
Near-Infrared-II Fluorescence Imaging of Tumors with Organic Small-Molecule Fluorophores
Guo, M., Hu, X., & Du, W. (2025) · Sensors · doi:10.3390/s25227080 · Cited by 11 · see citing works
Han, L., Wu, S.-P., Yang, J.-H., Mao, G., Chen, T., Wang, Q., & Zhang, G. (2024) · Microchemical Journal · doi:10.1016/j.microc.2024.111658 · Cited by 11 · see citing works
Yang, Z., Yang, H., Peng, Y., Jia, X., Liu, X., Liu, P., Zhang, S., & Li, J. (2026) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2026.217828 · Cited by 10 · see citing works
Wan, Q.-H., Gu, M., Shi, W., Tang, Y., Lu, Y., Xu, C., Chen, X., Wu, X., Gao, L., Han, D., et al. (2023) · Talanta · doi:10.1016/j.talanta.2023.125251 · Cited by 10 · see citing works
Zheng, F., Fan, D., Yao, H., Ding, J., Huang, S., Fang, Y., Dong, J. N., Chen, F., & Zeng, W. (2024) · ACS Materials Letters · doi:10.1021/acsmaterialslett.4c01400 · Cited by 7 · see citing works
Sadıkoğulları, B. C., & Özdemir, A. D. (2025) · Organic Letters · doi:10.1021/acs.orglett.5c02543 · Cited by 6 · see citing works
Jing, Y., Lu, J., Hong, J., Zhang, H., Yu, L., Guo, Y., Kong, Z., Pak, Y. L., Wang, Z., & Yoon, J. (2025) · Dyes and Pigments · doi:10.1016/j.dyepig.2025.113482 · Cited by 6 · see citing works
Jiao, L., Wang, Y., Wang, R., Luo, X., Xing, Y., Yu, F., & Dou, K. (2025) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2025.137731 · Cited by 5 · see citing works
Pan, Y., Lei, S., Liu, Q., Chen, K., Zhang, Y., Li, M., Liu, Y., Bai, M., Guo, H., Huang, P., et al. (2025) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2025.103027 · Cited by 5 · see citing works
Self-citationHu, J., Wang, C., Yao, D., & Wang, D. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.216709 · Cited by 5 · see citing works
Mei, X., Liu, Y., Liu, X., Ma, S., Wang, C., Wang, L., Miao, Q., Chen, P., Tang, B., & Chen, G. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.217441 · Cited by 4 · see citing works
Zhang, Y. X., Shan, L., Pan, Y., Zhao, C., Liu, Q., Wu, Y., Liu, Y., Li, M., Huang, P., & Lin, J. (2025) · Chinese Chemical Letters · doi:10.1016/j.cclet.2025.110977 · Cited by 2 · see citing works
Self-citationQuantitative Analysis of Glutathione Utilizing Highly Luminescent Gold Nanoclusters
He, W., Qu, Y., Wu, S., Lim, S. F., Mo, L., Mou, H., & Song, J. (2025) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37988 · Cited by 1 · see citing works
Fluorophores Used in NIRF Imaging
Lou, K., & Bai, J. (2025) · Springer eBooks · doi:10.1007/978-981-96-6875-5_3
TCF-based cyanine dyes: design strategies and phototheranostic applications
Wan, F., He, J., Liu, Y., Zhu, J., & Li, Z. L. (2026) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2026.218248
Leng, X., Guo, Z., & Sun, H.-L. (2026) · Talanta · doi:10.1016/j.talanta.2026.130833
- Authors
- Pan, Y., Lei, S., Zhang, J., Qu, J., Huang, P., & Lin, J.
- Affiliations
- Shenzhen University (CN)
- Corresponding author
- Lin, Jing
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-12-14
- Volume
- 93
- Issue
- 51
- Pages
- 17103-17109
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W4200202181
- Cited by
- 45
- References
- 35
- Citations by year
- 2026: 4 · 2025: 16 · 2024: 8 · 2023: 11 · 2022: 6
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2018YFA0704000, 2020YFA0908800)
- Basic Research Program of Shenzhen (JCYJ20180507182413022, JCYJ20200109105620482)
- Shenzhen Science and Technology Program (KQTD20190929172538530)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- glutathione, activatable fluorescent probes, in vivo imaging, fluorescence quenching, photostability, biothiol selectivity, let-7 microRNA
- MeSH terms
- Diagnostic Imaging, Fluorescence, Fluorescent Dyes, Glutathione, Humans
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