Germanium-Based Long-Conjugation Xanthene Fluorophores for Bioimaging in Optimal NIR-II Sub-Window

Jin Li , Qiming Xia , Jiayi Li , Xiaoming Yu , Zhe Feng , Yuhuang Zhang , Tianxiang Wu , Zhongmin Xu , Hui Lin , Jun Qian

Aggregate ›› 2025, Vol. 6 ›› Issue (11) : e70148

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Aggregate ›› 2025, Vol. 6 ›› Issue (11) :e70148 DOI: 10.1002/agt2.70148
RESEARCH ARTICLE
Germanium-Based Long-Conjugation Xanthene Fluorophores for Bioimaging in Optimal NIR-II Sub-Window
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Abstract

The near-infrared-IIx (NIR-IIx, 1400–1500 nm) sub-window theoretically surpasses the conventional near-infrared-II (NIR-II) region in optical imaging fidelity but requires luminophores with high brightness and stability. Herein, we present a germanium-engineered xanthene fluorophore (EGe5) featuring extended π-conjugation and a planarized core, as unequivocally resolved by single-crystal X-ray analysis. The vertically aligned methyl groups sterically hinder molecular vibration, while germanium's heavy-atom effect enhances radiative decay, collectively resulting in a 3.3% quantum yield in the NIR-II window and high NIR-IIx brightness. In addition, EGe5 retains nearly unchanged fluorescence intensity for over 12 h under harsh oxidative and reductive conditions. In vivo studies confirm its prolonged circulation time (>60 min) is enough for persistent NIR-IIx fluorescent angiography, which helps to identify the intestinal obstruction by tracing the diseased intestinal wall blood vessels. Furthermore, EGe5-PEG45 achieves rapid renal clearance and enables high-contrast excretory urography, dynamically tracking hydronephrosis progression in ureteral obstruction models. This work provides a molecular design paradigm for NIR-IIx probes and a versatile tool for minimally invasive diagnosis of gastrointestinal/urological diseases.

Keywords

extended conjugation / in vivo imaging / near-infrared-IIx / xanthene fluorophore

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Jin Li, Qiming Xia, Jiayi Li, Xiaoming Yu, Zhe Feng, Yuhuang Zhang, Tianxiang Wu, Zhongmin Xu, Hui Lin, Jun Qian. Germanium-Based Long-Conjugation Xanthene Fluorophores for Bioimaging in Optimal NIR-II Sub-Window. Aggregate, 2025, 6(11): e70148 DOI:10.1002/agt2.70148

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References

[1]

M. Tanzid, N. J. Hogan, A. Sobhani, et al., “Absorption-Induced Image Resolution Enhancement in Scattering Media,” ACS Photonics 3 (2016): 1787–1793.

[2]

J. A. Carr, M. Aellen, D. Franke, P. T. C. So, O. T. Bruns, and M. G. Bawendi, “Absorption by Water Increases Fluorescence Image Contrast of Biological Tissue in the Shortwave infrared,” Proceedings of the National Academy of Sciences 115 (2018): 9080–9085.

[3]

Y. Chang, H. Chen, X. Xie, et al., “Bright Tm3+-Based Downshifting Luminescence Nanoprobe Operating Around 1800 Nm for NIR-IIb and c Bioimaging,” Nature Communications 14 (2023): 1079.

[4]

Z.-H. Chen; X. Wang; M. Yang, et al., “An Extended NIR-II Superior Imaging Window From 1500 to 1900 Nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals,” Angewandte Chemie International Edition 62 (2023): e202311883.

[5]

Z. Feng; T. Tang; T. Wu, et al., “Perfecting and Extending the Near-Infrared Imaging Window,” Light: Science & Applications 10 (2021): 197.

[6]

F. Wang; F. Ren; Z. Ma, et al., “In Vivo Non-Invasive Confocal Fluorescence Imaging Beyond 1,700 Nm Using Superconducting Nanowire Single-Photon Detectors,” Nature Nanotechnology 17 (2022): 653–660.

[7]

Z. Fang; C. Wang; J. Yang, et al., “Oxyhaemoglobin Saturation NIR-IIb Imaging for Assessing Cancer Metabolism and Predicting the Response to Immunotherapy,” Nature Nanotechnology 19 (2024): 124–130.

[8]

Y. Yang; Y. Chen; P. Pei, et al., “Fluorescence-Amplified Nanocrystals in the Second Near-Infrared Window for In Vivo Real-Time Dynamic Multiplexed Imaging,” Nature Nanotechnology 18 (2023): 1195–1204.

[9]

X. Yu; Y. Ying; Z. Feng, et al., “Aggregation-Induced Emission Dots Assisted Non-Invasive Fluorescence Hysterography in Near-Infrared IIb Window,” Nano Today 39 (2021): 101235.

[10]

Z. Feng; Y. Li; S. Chen, et al., “Engineered NIR-II Fluorophores With Ultralong-Distance Molecular Packing for High-Contrast Deep Lesion Identification,” Nature Communications 14 (2023): 5017.

[11]

J. A. Carr; D. Franke; J. R. Caram, et al., “Shortwave Infrared Fluorescence Imaging With the Clinically Approved Near-Infrared Dye Indocyanine green,” Proceedings of the National Academy of Sciences 115 (2018): 4465–4470.

[12]

Z. Lei and F. Zhang, “Molecular Engineering of NIR-II Fluorophores for Improved Biomedical Detection,” Angewandte Chemie International Edition 60 (2021): 16294–16308.

[13]

R. Wei; Y. Dong; X. Wang, et al., “Rigid and Photostable Shortwave Infrared Dye Absorbing/Emitting Beyond 1200 Nm for High-Contrast Multiplexed Imaging,” Journal of the American Chemical Society 145 (2023): 12013–12022.

[14]

C. Yao; R. Wei; X. Luo, et al., “A Stable and Biocompatible Shortwave Infrared Nanoribbon for Dual-Channel In Vivo Imaging,” Nature Communications 16 (2025): 4.

[15]

X. Zhang; M. Liu; Y. Hu, et al., “Albumin-Chaperoned Deep-NIR Triarylmethane Dyes for High-Contrast In Vivo Imaging and Photothermal Therapy,” Advanced Materials 37 (2025): 2411515.

[16]

Z. Hu; C. Fang; B. Li, et al., “First-in-Human Liver-Tumour Surgery Guided by Multispectral Fluorescence Imaging in the Visible and Near-Infrared-I/II Windows,” Nature Biomedical Engineering 4 (2020): 259–271.

[17]

X. Yu; Z. Feng; Z. Cai, et al., “Deciphering of Cerebrovasculatures via ICG-Assisted NIR-II Fluorescence Microscopy,” Journal of Materials Chemistry B 7 (2019): 6623–6629.

[18]

J. Li; Z. Feng; X. Yu; D. Wu; T. Wu; and J. Qian, “Aggregation-Induced Emission Fluorophores Towards the Second Near-Infrared Optical Windows With Suppressed Imaging Background,” Coordination Chemistry Reviews 472 (2022): 214792.

[19]

W. Wu; K. Yan; Z. He, et al., “2X-Rhodamine: A Bright and Fluorogenic Scaffold for Developing Near-Infrared Chemigenetic Indicators,” Journal of the American Chemical Society 146 (2024): 11570–11576.

[20]

X.-X. Zhang; F. Yang; X. Zhao, et al., “Dihydropyridopyrazine Functionalized Xanthene: Generating Stable NIR Dyes With Small-Molecular Weight by Enhanced Charge Separation,” Angewandte Chemie International Edition 63 (2024): e202410666.

[21]

X. Zhao; F. Zhang, and Z. Lei, “The Pursuit of Polymethine Fluorophores With NIR-II Emission and High Brightness for In Vivo Applications,” Chemical Science 13 (2022): 11280–11293.

[22]

M. Dai; Y. J. Yang; S. Sarkar; and K. H. Ahn, “Strategies to Convert Organic Fluorophores Into Red/Near-Infrared Emitting Analogues and Their Utilization in Bioimaging Probes,” Chemical Society Reviews 52 (2023): 6344–6358.

[23]

L.-N. Zhang; S.-Y. Chen; L. Shi, et al., “De Novo Construction of pKa -Tunable Xanthene Molecules for pH Sensitive Fluorescence Navigation,” Advanced Functional Materials 35 (2025): 2412595.

[24]

L. Guttieres; L. Vannelli; S. Demortiere, et al., “Fluorescein Angiography as a Surrogate Marker of Disease Activity in Susac Syndrome,” Neurology: Neuroimmunology & Neuroinflammation 12 (2025): e200379.

[25]

Z. Lei; X. Li; X. Luo, et al., “Bright, Stable, and Biocompatible Organic Fluorophores Absorbing/Emitting in the Deep Near-Infrared Spectral Region,” Angewandte Chemie International Edition 56 (2017): 2979–2983.

[26]

J. Li; Y. Dong, R. Wei, et al., “Stable, Bright, and Long-Fluorescence-Lifetime Dyes for Deep-Near-Infrared Bioimaging,” Journal of the American Chemical Society 144 (2022): 14351–14362.

[27]

I. Baiu and M. T. Hawn, “Small Bowel Obstruction,” JAMA 319 (2018): 2146.

[28]

F. Catena; B. De Simone; F. Coccolini; S. Di Saverio; M. Sartelli; and L. Ansaloni, “Bowel Obstruction: A Narrative Review for All Physicians,” World Journal of Emergency Surgery 14 (2019): 20.

[29]

R. Salman; V. J. Seghers; D. M. Schiess, et al., “Ultrasound Imaging of Bowel Obstruction in Infants and Children,” La Radiologia Medica 129 (2024): 1241–1251.

[30]

O. B. Alese; S. Kim; Z. Chen; T. K. Owonikoko; and B. F. El-Rayes, “Management Patterns and Predictors of Mortality Among US Patients With Cancer Hospitalized for Malignant Bowel Obstruction,” Cancer 121 (2015): 1772–1778.

[31]

M. J. Lee; A. E. Sayers; T. R. Wilson, et al., “Current Management of Small Bowel Obstruction in the UK: Results From the National Audit of Small Bowel Obstruction Clinical Practice Survey,” Colorectal Disease 20 (2018): 623–630.

[32]

S. Mercadante, “Management of Malignant Bowel Obstruction,” Lancet Gastroenterol 9 (2024): 14.

[33]

S. Ghosh; A. Kilcoyne; A. Kambadakone; M. G. Harisinghani; N. Nakrour; and A. S. Shenoy-Bhangle, “Urologic Imaging of Collecting System and Ureters: Cancers and Mimics,” Urologic Clinics 52 (2025): 91–109.

[34]

C. Würth; M. Grabolle; J. Pauli; M. Spieles; and U. Resch-Genger, “Relative and Absolute Determination of Fluorescence Quantum Yields of Transparent Samples,” Nature Protocols 8 (2013): 1535–1550.

[35]

G. Sheldrick, “SHELXT—Integrated Space-Group and Crystal-Structure Determination,” Foundations of Crystallography 71 (2015): 3–8.

[36]

O. V. Dolomanov; L. J. Bourhis; R. J. Gildea; J. A. K. Howard; and H. Puschmann, “OLEX2: A Complete Structure Solution, Refinement and Analysis Program,” Journal of Applied Crystallography 42 (2009): 339–341.

[37]

S. E. Ha; L. Wei; B. G. Jorgensen, et al., “A Mouse Model of Intestinal Partial Obstruction,” Journal of Visualized Experiments: JoVE 133 (2018): e57381.

[38]

R. L. Chevalier; M. S. Forbes, and B. A. Thornhill, “Ureteral Obstruction as a Model of Renal Interstitial Fibrosis and Obstructive Nephropathy,” Kidney International 75 (2009): 1145–1152.

[39]

H.-H. Chi; K.-F. Hua; Y.-C. Lin, et al., “IL-36 Signaling Facilitates Activation of the NLRP3 Inflammasome and IL-23/IL-17 Axis in Renal Inflammation and Fibrosis,” Journal of the American Society of Nephrology 28 (2017): 2022–2037.

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2025 The Author(s). Aggregate published by SCUT, AIEI and John Wiley & Sons Australia, Ltd.

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