NIR‐II Fluorescent Protein Created by In Situ Albumin‐Tagging for Sensitive and Specific Imaging of Blood‐Brain Barrier Disruption
Open accessAbstract
Imaging albumin in vivo is a reliable strategy to visualize blood‐brain barrier (BBB) disruption by detecting the dye‐labeled albumin leaking into brain parenchyma. Although Evans Blue (EB) and indocyanine green (ICG) dyes have been applied to assess BBB impairment, their naked‐eye observation or near‐infrared‐I (NIR‐I) imaging window limit the imaging sensitivity and contrast for this promising “albumin‐based” strategy. Herein, an albumin‐specific tagged near‐infrared‐II (NIR‐II) probe is engineered as a chromophore to construct fluorescent proteins (FPs) in situ for assessing BBB disruption in stroke. The optimized chromophore, C7‐1080, can covalently bind to albumin through nucleophilic substitution, forming FPs without adjuvant. Notably, the albumin effectively acts as a brightness enhancer and stability regulator for chromophores through the tight clamping effect. Theoretical simulation, proteomics, and protein mutation techniques are employed to investigate the binding behavior between albumin and chromophore. The in situ NIR‐II FPs construction strategy facilitates high‐precision dual‐channel imaging of BBB disruption and cerebral vessels during ischemic stroke when combined with the IR‐808Ac probe. Overall, the in situ albumin‐specific tag holds promise for diagnosing and monitoring strokes, presenting a tool for investigating the progression and therapeutic responses of related diseases.
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When paired with the albumin-escaping probe IR-800Ac, C7-1080 enabled real-time dual-channel imaging of BBB leakage and cerebral vessels.
“When paired with the albumin-escaping probe IR-800Ac, C7-1080 enabled real-time dual-channel imaging of BBB leakage and cerebral vessels.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [107]
The Results and Discussion (Figure 6j) report dual-channel imaging of BBB leakage with C7-1080 and cerebral vessels with an albumin-escaping probe, including real-time vascular imaging. However, the probe is named IR-808Ac throughout the passage, not IR-800Ac; no page number is provided in our copy. (LLM, conf=0.92)
Experimental — accuracy not yet measuredIn the photothrombotic stroke model, C7-1080 enabled high-sensitivity detection of BBB damage within 10 min post injection, with results showing strong correlation with TTC and EB staining.
“In the photothrombotic stroke (PTS) model, the probe enabled high-sensitivity detection of BBB damage within just 10 min post injection, with results showing strong correlation with both 2,3,5-triphenyltetrazolium chloride (TTC) and EB staining.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [107]
Zhu et al. developed an albumin-specific tagged probe C7-1080 via a molecular side group engineering strategy.
“Zhu et al. developed an albumin-specific tagged probe, C7-1080, via a molecular side group engineering strategy (Fig. 14a)107.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [107]
C7-1080 exhibited superior fluorescence brightness and photostability compared to ICG.
“C7-1080 exhibited superior fluorescence brightness and photostability compared to ICG.”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [107]
In situ albumin-specific labeling showed great potential for stroke diagnosis and monitoring.
“In general, in situ albumin-specific labeling showed great potential for stroke diagnosis and monitoring”
From Organic small-molecule NIR-II fluorophores for tumor phototheranostics (2026) · cites this paper as [107]
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Cited by
Sorted by citations
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
- Authors
- Xu, J., Du, Y., Zhu, N., Li, J., Zhang, Y., Zhou, D., & Zhu, S.
- Affiliations
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Corresponding author
- Xu, Jiajun
- Li, Jia
- Zhou, Ding
- Zhu, Shoujun
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2025-02-25
- Volume
- 12
- Issue
- 16
- Pages
- e2500443-e2500443
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC12021084
- OpenAlex
- W4407987665
- Cited by
- 10
- References
- 58
- Citations by year
- 2026: 6 · 2025: 4
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Program of China (2022YFC2601900)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- blood-brain barrier disruption, stroke imaging, ischemic stroke, dual-channel imaging, cerebral vasculature, Evans blue, indocyanine green, chromophore stability
- MeSH terms
- Albumins, Animals, Blood-Brain Barrier, Fluorescent Dyes, Humans, Luminescent Proteins, Spectroscopy, Near-Infrared, Mice
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