Xanthene-Based NIR-II Dyes for In Vivo Dynamic Imaging of Blood Circulation
Abstract
Fluorescence bioimaging through the second near-infrared window (NIR-II, 1000-1700 nm) has attracted much attention due to its deep penetration and high contrast. However, exploring new fluorescent materials, especially small molecular fluorophores with long wavelength and high brightness, is still quite challenging. By expanding π-conjugation and enhancing the intramolecular charge transfer effect, herein we report a series of new xanthene-based NIR-II dyes, named VIXs. Among these dyes, VIX-4 exhibits the best performance with fluorescence emission at 1210 nm and high brightness and has been used for dynamically imaging the blood flow of mice at 200 fps. By virtue of high spatiotemporal resolution of the dynamic imaging, we can distinguish directly the artery and vein through the blood flow direction and measure the blood flow volume by the videos. This study provides not only an effective tool for high spatial and temporal resolution bioimaging but also a new and promising conjugated skeleton for NIR-II dyes.
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The xanthene scaffold consists of three fused rings: a central oxygen-containing six-membered heterocycle symmetrically flanked by benzene rings.
“The xanthene scaffold consists of three fused rings: a central oxygen-containing six-membered heterocycle symmetrically flanked by benzene rings170.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
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 [170]
The primary reactivity of xanthene is located at the C9 position, often functionalized with spirocycles or electron-donating groups, whereas the 3,6-positions typically carry amino or hydroxy substituents.
“The primary reactivity is located at the C9 position, often functionalized with spirocycles or electron-donating groups, whereas the 3, 6-positions typically carry amino (-NH2) or hydroxy (-OH) substituents”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
Julolidine-substituted VIX-4 showed the most pronounced red-shift and significantly enhanced brightness, reaching emission at 1210 nm.
“Among them, julolidine-substituted VIX-4 showed the most pronounced red-shift and significantly enhanced brightness, reaching emission at 1210 nm.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
VIX-4 enabled high-speed blood flow imaging in mice at up to 200 fps.
“enabling high-speed blood flow imaging in mice at up to 200 fps.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
Ma et al. reported a series of xanthene dyes VIXs by introducing para-substituted styryl groups of progressively stronger electron-donating ability.
“Similarly, Ma et al. reported a series of xanthene dyes VIXs by introducing para-substituted styryl groups of progressively stronger electron-donating ability170.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
VIX-4 exhibited a large Stokes shift and six-fold higher brightness compared with classical BBTD dyes.
“Importantly, VIX-4 exhibited a large Stokes shift and six-fold higher brightness compared with classical BBTD dyes”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
VIX-4 exhibited a maximum fluorescence emission at 1210 nm and high brightness in dichloromethane solution.
“VIX-4 exhibited a maximum fluorescence emission at 1210 nm and high brightness in dichloromethane solution.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
Ma et al. developed a novel xanthene-based NIR-II dye, VIX-4, for dynamic imaging of blood circulation in living organisms.
“Ma et al. developed a novel xanthene-based NIR-II dye, VIX-4, for dynamic imaging of blood circulation in living organisms (Fig. 18a)170.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [170]
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- Authors
- Liu, D., He, Z., Zhao, Y., Yang, Y., Shi, W., Li, X., & Ma, H.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shi, Wen
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-10-11
- Volume
- 143
- Issue
- 41
- Pages
- 17136-17143
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W3205046513
- Cited by
- 217
- References
- 58
- Citations by year
- 2026: 37 · 2025: 40 · 2024: 49 · 2023: 45 · 2022: 44 · 2021: 2
- FWCI
- 10.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (21775152, 21820102007, 21922412, 22074151, 22174148)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- xanthene, second near-infrared window, small-molecule fluorophores, intramolecular charge transfer, π-conjugation, blood flow imaging, blood flow direction
- MeSH terms
- Animals, Blood Circulation, Fluorescent Dyes, Humans, Infrared Rays, Xanthenes, Molecular Structure, Mice, Optical Imaging
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