A General Strategy for Development of Activatable NIR‐II Fluorescent Probes for In Vivo High‐Contrast Bioimaging
Abstract
Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Xanthene dyes, particularly rhodamines and fluoresceins, have attracted considerable attention in biomedical imaging owing to outstanding photophysical properties including high molar absorptivity, excellent photostability, facile functionalization, and tunable emission.
“Xanthene dyes, particularly rhodamines and fluoresceins, have attracted considerable attention in biomedical imaging owing to their outstanding photophysical properties, including high molar absorptivity, excellent photostability, facile functionalization, and tunable emission”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [171]
Cites
Aggregation-Induced Emission: Together We Shine, United We Soar!
Mei, J., Leung, N. L. C., Kwok, R. T. K., Lam, J. W. Y., & Tang, B. Z. (2015) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00263 · Cited by 8,270 · see citing works
Renal clearance of quantum dots
Soo Choi, H., Liu, W., Misra, P., Tanaka, E., Zimmer, J. P., Itty Ipe, B., Bawendi, M. G., & Frangioni, J. V. (2007) · Nature Biotechnology · doi:10.1038/nbt1340 · Cited by 4,476 · 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
A small-molecule dye for NIR-II imaging
Antaris, A. L., Chen, H., Cheng, K., Sun, Y., Hong, G., Qu, C., Diao, S., Deng, Z., Hu, X., Zhang, B., et al. (2016) · Nature Materials · doi:10.1038/nmat4476 · Cited by 1,778 · see citing works
Self-citationATP drives lamina propria TH17 cell differentiation
Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., et al. (2008) · Nature · doi:10.1038/nature07240 · Cited by 1,089 · see citing works
Yang, Y., Yook, K.-J., & Tae, J. (2005) · Journal of the American Chemical Society · doi:10.1021/ja054855t · Cited by 1,046 · 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
Multifunctional in vivo vascular imaging using near-infrared II fluorescence
Hong, G., Lee, J. C., Robinson, J. T., Raaz, U., Xie, L., Huang, N. F., Cooke, J. P., & Dai, H. (2012) · Nature Medicine · doi:10.1038/nm.2995 · Cited by 995 · see citing works
Real‐time identification of liver cancers by using indocyanine green fluorescent imaging
Ishizawa, T., Fukushima, N., Shibahara, J., Masuda, K., Tamura, S., Aoki, T., Hasegawa, K., Beck, Y., Fukayama, M., & Kokudo, N. (2009) · Cancer · doi:10.1002/cncr.24291 · Cited by 857 · see citing works
Zhang, Y., Hong, G., Zhang, Y., Chen, G., Li, F., Dai, H., & Wang, Q. (2012) · ACS Nano · doi:10.1021/nn301218z · Cited by 765 · see citing works
Carr, J. A., Franke, D., Caram, J. R., Perkinson, C. F., Saif, M., Askoxylakis, V., Datta, M., Fukumura, D., Jain, R. K., Bawendi, M. G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718917115 · Cited by 721 · see citing works
Li, B., Lu, L., Zhao, M., Lei, Z., & Zhang, F. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201801226 · Cited by 658 · see citing works
Shuhendler, A. J., Pu, K., Cui, L., Uetrecht, J., & Rao, J. (2014) · Nature Biotechnology · doi:10.1038/nbt.2838 · Cited by 623 · see citing works
Yuan, L., Lin, W., Yang, Y., & Chen, H. (2011) · Journal of the American Chemical Society · doi:10.1021/ja209292b · Cited by 563 · see citing works
Self-citationDonor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent Performance
Yang, Q., Hu, Z., Zhu, S., Ma, R., Ma, H., Ma, Z., Wan, H., Zhu, T., Jiang, Z., Liu, W., et al. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.7b10334 · Cited by 554 · see citing works
Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging
Ding, F., Zhan, Y., Lu, X., & Sun, Y. (2018) · Chemical Science · doi:10.1039/c8sc01153b · Cited by 540 · see citing works
Anti-quenching NIR-II molecular fluorophores for in vivo high-contrast imaging and pH sensing
Wang, S., Fan, Y., Li, D., Sun, C., Lei, Z., Lu, L., Wang, T., & Zhang, F. (2019) · Nature Communications · doi:10.1038/s41467-019-09043-x · Cited by 510 · see citing works
A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues
Wan, H., Yue, J., Zhu, S., Uno, T., Zhang, X., Yang, Q., Yu, K., Hong, G., Wang, J., Li, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03505-4 · Cited by 450 · see citing works
Self-citationA General Method To Increase Stokes Shift by Introducing Alternating Vibronic Structures
Ren, T., Xu, W., Zhang, W., Zhang, X.-X., Wang, Z.-Y., Xiang, Z., Yuan, L., & Zhang, X. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b04404 · Cited by 445 · see citing works
Self-citationMolecular Mechanism of NLRP3 Inflammasome Activation
Jin, C., & Flavell, R. A. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9440-3 · Cited by 440 · see citing works
Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging
Zhang, M., Yue, J., Cui, R., Ma, Z., Wan, H., Wang, F., Zhu, S., Zhou, Y., Kuang, Y., Zhong, Y., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1806153115 · Cited by 432 · see citing works
Flavylium Polymethine Fluorophores for Near‐ and Shortwave Infrared Imaging
Cosco, E. D., Caram, J. R., Bruns, O. T., Franke, D., Day, R. A., Farr, E. P., Bawendi, M. G., & Sletten, E. M. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201706974 · Cited by 415 · see citing works
Soft fluorescent nanomaterials for biological and biomedical imaging
Peng, H., & Chiu, D. T. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00294f · Cited by 408 · see citing works
Traumatic Brain Injury Imaging in the Second Near‐Infrared Window with a Molecular Fluorophore
Zhang, X., Wang, H., Antaris, A. L., Li, L., Diao, S., Ma, R., Nguyen, A., Hong, G., Ma, Z., Wang, J., et al. (2016) · Advanced Materials · doi:10.1002/adma.201600706 · Cited by 386 · see citing works
Self-citationLei, Z., Sun, C., Pei, P., Wang, S., Li, D., Zhang, X., & Zhang, F. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201904182 · Cited by 362 · see citing works
Self-citationOushiki, D., Kojima, H., Terai, T., Arita, M., Hanaoka, K., Urano, Y., & Nagano, T. (2010) · Journal of the American Chemical Society · doi:10.1021/ja910090v · Cited by 361 · see citing works
Zhu, S., Hu, Z., Tian, R., Yung, B. C., Yang, Q., Zhao, S., Kiesewetter, D. O., Niu, G., Sun, H., Antaris, A. L., et al. (2018) · Advanced Materials · doi:10.1002/adma.201802546 · Cited by 349 · see citing works
Cheng, D., Peng, J., Lv, Y., Su, D., Liu, D., Chen, M. Y., Yuan, L., & Zhang, X. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b01374 · Cited by 310 · see citing works
Self-citationNovel benzo-bis(1,2,5-thiadiazole) fluorophores for in vivo NIR-II imaging of cancer
Sun, Y., Qu, C., Chen, H., He, M., Tang, C. C., Shou, K., Hong, S., Yang, M., Jiang, Y., Ding, B., et al. (2016) · Chemical Science · doi:10.1039/c6sc01561a · Cited by 294 · see citing works
Zhao, M., Li, B., Wu, Y., He, H., Zhu, X., Zhang, H., Dou, C., Feng, L., Fan, Y., & Zhang, F. (2020) · Advanced Materials · doi:10.1002/adma.202001172 · Cited by 237 · see citing works
An Activatable NIR‐II Nanoprobe for In Vivo Early Real‐Time Diagnosis of Traumatic Brain Injury
Li, C., Li, W., Liu, H., Zhang, Y., Chen, G., Li, Z., & Wang, Q. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201911803 · Cited by 216 · see citing works
Ding, B., Xiao, Y., Zhou, H., Zhang, X., Qu, C., Xu, F., Deng, Z., Cheng, Z., & Hong, X. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01682 · Cited by 215 · see citing works
Self-citationOuyang, J., Sun, L., Zeng, Z., Zeng, C., Zeng, F., & Wu, S. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201913149 · Cited by 212 · see citing works
Lei, Z., Sun, C., Pei, P., Wang, S., Li, D., Zhang, X., & Zhang, F. (2019) · Angewandte Chemie · doi:10.1002/ange.201904182 · Cited by 209 · see citing works
Self-citationLi, D., Wang, S., Lei, Z., Sun, C., El‐Toni, A. M., Alhoshan, M. S., Fan, Y., & Zhang, F. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b00317 · Cited by 191 · see citing works
Dang, X., Gu, L., Qi, J., Correa, S., Zhang, G., Belcher, A. M., & Hammond, P. T. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521175113 · Cited by 190 · see citing works
Ecto 5′-Nucleotidase and Nonspecific Alkaline Phosphatase
Picher, M., Burch, L. H., Hirsh, A. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300569200 · Cited by 184 · see citing works
Verbeek, F. P. R., van der Vorst, J. R., Schaafsma, B. E., et al. (2013) · The Journal of Urology · doi:10.1016/j.juro.2013.02.3187 · Cited by 176 · see citing works
Egawa, T., Koide, Y., Hanaoka, K., Komatsu, T., Terai, T., & Nagano, T. (2011) · Chemical Communications · doi:10.1039/c1cc00078k · Cited by 172 · see citing works
Stability enhancement of fluorophores for lighting up practical application in bioimaging
Wu, X., & Zhu, W. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00152d · Cited by 145 · see citing works
Tan, G., Pan, S., Li, J., Dong, X., Kang, K., Zhao, M., Jiang, X. L., Kanwar, J. R., Qiao, H., Jiang, H., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025943 · Cited by 140 · see citing works
Li, B., Lu, L., Zhao, M., Lei, Z., & Zhang, F. (2018) · Angewandte Chemie · doi:10.1002/ange.201801226 · Cited by 137 · see citing works
Ren, T., Wen, S., Wang, L., Peng, L., Xiong, B., Yuan, L., & Zhang, X. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c00506 · Cited by 107 · see citing works
Self-citationSong, X., Johnson, A., & Foley, J. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8075617 · Cited by 99 · see citing works
Xu, S., Liu, H., Chen, L., Yuan, J., Liu, Y., Teng, L., Huan, S., Yuan, L., Zhang, X., & Tan, W. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b11245 · Cited by 75 · see citing works
Self-citationLiu, X., Lai, H., Peng, J., et al. (2019) · Small · doi:10.1002/smll.201902737 · Cited by 67 · see citing works
Self-citationFlavylium Polymethine Fluorophores for Near‐ and Shortwave Infrared Imaging
Cosco, E. D., Caram, J. R., Bruns†, O. T., Franke, D., Day, R. A., Farr, E. P., Bawendi, M. G., & Sletten, E. M. (2017) · Angewandte Chemie · doi:10.1002/ange.201706974 · Cited by 65 · see citing works
Ouyang, J., Sun, L., Zeng, Z., Zeng, C., Zeng, F., & Wu, S. (2019) · Angewandte Chemie · doi:10.1002/ange.201913149 · Cited by 60 · see citing works
An Activatable NIR‐II Nanoprobe for In Vivo Early Real‐Time Diagnosis of Traumatic Brain Injury
Li, C., Li, W., Liu, H., Zhang, Y., Chen, G., Li, Z., & Wang, Q. (2019) · Angewandte Chemie · doi:10.1002/ange.201911803 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
In vivo NIR-II fluorescence imaging for biology and medicine
Wang, F., Zhong, Y., Bruns, O., Liang, Y., & Dai, H. (2024) · Nature Photonics · doi:10.1038/s41566-024-01391-5 · Cited by 564 · see citing works
Near infrared fluorescent probes for detecting and imaging active small molecules
Ding, C., & Ren, T. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215080 · Cited by 247 · see citing works
Self-citationXanthene-Based NIR-II Dyes for <i>In Vivo</i> Dynamic Imaging of Blood Circulation
Liu, D., He, Z., Zhao, Y., Yang, Y., Shi, W., Li, X., & Ma, H. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c07711 · Cited by 217 · see citing works
Qin, Z., Ren, T., Zhou, H., Zhang, X., He, L., Li, Z., Zhang, X., & Yuan, L. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202201541 · Cited by 140 · see citing works
Self-citationYang, Y., Sun, C., Wang, S., Yan, K., Zhao, M., Wu, B., & Zhang, F. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202117436 · Cited by 139 · see citing works
Song, S., Wang, Y., Zhao, Y., Huang, W., Zhang, F., Zhu, S., Wu, Q., Fu, S., Tang, B. Z., & Wang, D. (2022) · Matter · doi:10.1016/j.matt.2022.06.030 · Cited by 133 · see citing works
Ma, D., Bian, H., Gu, M., Wang, L., Chen, X., & Peng, X. (2024) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2024.215677 · Cited by 124 · see citing works
Dou, K., Feng, W., Fan, C., Cao, Y., Xiang, Y., & Liu, Z. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.0c04990 · Cited by 67 · see citing works
Swamy, M. M. M., Murai, Y., Monde, K., Tsuboi, S., & Jin, T. (2021) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.1c00253 · Cited by 59 · see citing works
Tian, Y., Chen, Z., Liu, S., Wu, F., Cao, W., Pang, D., & Xiong, H. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202309768 · Cited by 57 · see citing works
Ye, M., Xiang, Y., Gong, J., Wang, X., Mao, Z., & Liu, Z. (2023) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.130612 · Cited by 37 · 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
Self-citationNear-infrared II theranostic agents for the diagnosis and treatment of Alzheimer’s disease
Zhou, C., Zeng, F., Yang, H., Liang, Z., Xu, G., Li, X., Liu, X., & Yang, J. (2024) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-024-06690-1 · Cited by 14 · see citing works
- Authors
- Ren, T., Wang, Z., Xiang, Z., Lu, P., Lai, H., Yuan, L., Zhang, X., & Tan, W.
- Affiliations
- Hunan University (CN)
- Molecular Science and Biomedicine Laboratory (MBL) State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2020-11-03
- Volume
- 60
- Issue
- 2
- Pages
- 800-805
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W3086680449
- Cited by
- 273
- References
- 49
- Citations by year
- 2026: 25 · 2025: 40 · 2024: 46 · 2023: 61 · 2022: 73 · 2021: 27 · 2020: 1
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Key Technologies Research and Development Program (2019YFA0210100)
- National Natural Science Foundation of China (21890744, 21622504, 21877029)
- National Postdoctoral Program for Innovative Talents (BX20190110)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- activatable probes, polymethine dyes, pH sensing, ATP detection, metal ion sensing, drug-induced liver injury, real-time monitoring, carboxyl groups
- MeSH terms
- Animals, Blood Vessels, Contrast Media, Fluorescent Dyes, Indocyanine Green, Lymph Nodes, Polymers, Spectroscopy, Near-Infrared, Mice, Chemical and Drug Induced Liver Injury, Optical Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review