A Class of Activatable NIR‐II Photoacoustic Dyes for High‐Contrast Bioimaging
Abstract
Photoacoustic (PA) imaging is emerging as one of the important non-invasive imaging techniques in biomedical research. Small molecule- second near-infrared window (NIR-II) PA dyes combined with imaging data can provide comprehensive and in-depth in vivo physiological and pathological information. However, the NIR-II PA dyes usually exhibit "always-on" properties due to the lack of a readily optically tunable group, which hinders the further applications in vivo. Herein, a novel class of dyes GX have been designed and synthesized as an activatable NIR-II PA platform, in which the absorption/emission wavelength of GX-5 extends up to 1082/1360 nm. Importantly, the GX dyes have a strong tissue penetration depth and high-resolution for the mouse vasculature structures in NIR-II PA 3D imaging and high signal-to-noise ratio in NIR-II fluorescence (FL) imaging. Furthermore, to demonstrate the applicability of GX dyes, the first NIR-II PA probe GX-5-CO activated by carbon monoxide (CO) was engineered and employed to reveal the enhancement of the CO levels in the hypertensive mice by high-contrast NIR-II PA and FL imaging. We expect that many derivatives of GX dyes will be developed to afford versatile NIR-II PA platforms for designing a wide variety activatable NIR-II PA probes as biomedical tools.
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Rational molecular engineering of the xanthene scaffold can effectively endow dyes with responsive and activatable properties.
“Recent progress has demonstrated that rational molecular engineering of the xanthene scaffold can effectively endow dyes with responsive and activatable properties173,184.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
Substituent engineering on the xanthene framework enabled systematic spectral red-shifting.
“Substituent engineering on the xanthene framework enabled systematic spectral red-shifting”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
GX-5-CO achieved high-contrast NIR-II PA/FL imaging of endogenous CO in a murine hypertension model.
“which achieved high-contrast NIR-II PA/FL imaging of endogenous CO in a murine hypertension model.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
The optimized GX-5 scaffold exhibited absorption/emission maxima at 1082/1360 nm.
“the optimized GX-5 scaffold exhibited absorption/emission maxima at 1082/1360 nm.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
Lin et al. established the GX dye platform by coupling carboxy-controlled spirocyclization of rhodamine dyes with NIR-II absorption/emission characteristics.
“Lin et al. established the GX dye platform by coupling the carboxy-controlled spirocyclization of rhodamine dyes with NIR-II absorption/emission characteristics (Fig. 10a)184.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
GX-5 modularity allowed construction of a carbon monoxide-activatable probe GX-5-CO.
“its modularity allowed the construction of a carbon monoxide-activatable probe (GX-5-CO)”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [184]
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Song, Y., Tong, X., Han, Y., & Zhang, Q. (2025) · Aggregate · doi:10.1002/agt2.680 · Cited by 47 · see citing works
Advances on fluorescence bioimaging and photo-mediated therapy of NIR-II small molecule dyes
Zhang, W., Laraib, Huo, F., & Yin, C. (2025) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2025.216587 · Cited by 26 · 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
“9 and Table 4) 170 – 184 .”
- Authors
- Li, J., Wang, J., Xu, L., Chi, H., Liang, X., Yoon, J., & Lin, W.
- Affiliations
- Guangxi University (CN)
- Ewha Womans University (KR)
- Corresponding author
- Yoon, Juyoung
- Lin, Weiying
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2023-10-27
- Volume
- 63
- Issue
- 2
- Pages
- e202312632-e202312632
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W4387729089
- Cited by
- 58
- References
- 0
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 16
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (21877048, 22077048, and 22277014)
- Natural Science Foundation of Guangxi Zhuang Autonomous Region (2021GXNSFDA075003, AD21220061)
- National Research Foundation of Korea (RS2023-00217701, 2022M3E5F3080873)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Keywords
- activatable probes, carbon monoxide detection, photoacoustic imaging, NIR-II fluorescence imaging, tissue penetration depth, vascular imaging, hypertension, small-molecule dyes
- MeSH terms
- Animals, Fluorescent Dyes, Spectrum Analysis, Mice, Photoacoustic Techniques, Optical Imaging
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