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Unimolecular near-infrared chemiluminescent reporter for cascaded multiplex imaging of ischemia-reperfusion injury in the liver-kidney axis

Author

Listed:
  • Bankang Ruan

    (Sun Yat-sen University)

  • Weiliang Deng

    (Sun Yat-sen University)

  • Jingjing Che

    (Sun Yat-sen University)

  • Shujuan Yi

    (Sun Yat-sen University)

  • Jie Liu

    (University of Chinese Academy of Sciences)

  • Weiping Xu

    (University of Chinese Academy of Sciences)

  • Yuyan Jiang

    (Stanford University School of Medicine)

  • Ya zhou

    (Sun Yat-sen University)

  • Pan Xie

    (Army Medical University)

  • Huhai Zhang

    (Army Medical University)

  • Hongwen Zhao

    (Army Medical University)

  • Jiaguo Huang

    (Sun Yat-sen University)

Abstract

Acute kidney injury (AKI) frequently arises as a complication of hepatic ischemia-reperfusion injury (HIRI), yet simultaneous optical imaging of both remains challenging due to the lack of unimolecular dual-responsive probes. Herein, we report a library of hemicyanine-based chemiluminophores (HCLs) with tunable emission to second near-infrared window (725 − 1025 nm) achieved by integrating bicyclic dioxetane onto hemicyanine skeletons to develop multiple-responsive chemiluminescent probes. HCL1 and HCL5 respectively emitting at 725 nm and 1025 nm are selected to construct a cascaded activatable reporter CAR for crosstalk-free duplex chemiluminescence imaging of interlinked biomarkers. Following systemic injection to male mice, CAR preferentially accumulates in the liver and reports HIRI-associated superoxide anion (O2•−), which initiates self-fragmentation and liberates the secondary reporter KIR into kidneys to report AKI-associated N-acetyl-β-D-glucosaminidase (NAG). Such mechanism allows CAR to serve as a reservoir for gradual release of AKI reporters, providing a significantly prolonged imaging window compared to co-administering separate probes. CAR further permits remote detection of HIRI-induced AKI via urinalysis. This study not only offers a powerful tool for simultaneous detection of HIRI and HIRI-induced AKI, but also highlights a unimolecular probe design for ultrasensitive detection of deeply-seated intercorrelated diseases.

Suggested Citation

  • Bankang Ruan & Weiliang Deng & Jingjing Che & Shujuan Yi & Jie Liu & Weiping Xu & Yuyan Jiang & Ya zhou & Pan Xie & Huhai Zhang & Hongwen Zhao & Jiaguo Huang, 2025. "Unimolecular near-infrared chemiluminescent reporter for cascaded multiplex imaging of ischemia-reperfusion injury in the liver-kidney axis," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62348-y
    DOI: 10.1038/s41467-025-62348-y
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    References listed on IDEAS

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    1. Yue Jiang & Min Zhao & Jia Miao & Wan Chen & Yuan Zhang & Minqian Miao & Li Yang & Qing Li & Qingqing Miao, 2024. "Acidity-activatable upconversion afterglow luminescence cocktail nanoparticles for ultrasensitive in vivo imaging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Renye Yue & Zhe Li & Huiyi Liu & Youjuan Wang & Yuhang Li & Rui Yin & Baoli Yin & Haisheng Qian & Heemin Kang & Xiaobing Zhang & Guosheng Song, 2024. "Imaging-guided companion diagnostics in radiotherapy by monitoring APE1 activity with afterglow and MRI imaging," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Lingfei Lu & Benhao Li & Suwan Ding & Yong Fan & Shangfeng Wang & Caixia Sun & Mengyao Zhao & Chun-Xia Zhao & Fan Zhang, 2020. "NIR-II bioluminescence for in vivo high contrast imaging and in situ ATP-mediated metastases tracing," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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