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Successively activatable ultrasensitive probe for imaging tumour acidity and hypoxia

Nature Biomedical Engineering volume 1, Article number: 0057 (2017) Cite this article

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Abstract

Molecular imaging probes for biomarker-based diagnosis typically target, with limited sensitivity, a single molecular process or event in a complex biological system. Here, we show that the macromolecular near-infrared poly(ethylene glycol)-conjugated iridium (iii) complex can be designed to successively respond to tumour acidity and hypoxia while amplifying detection sensitivity via signal propagation. We used the probe to detect, by near-infrared imaging, primary tumours and metastatic tumour nodules as small as 1 mm in mice, and to measure the in vivo metabolic rate of cancer cells. We anticipate that probes for imaging coupled biological events with amplified detection sensitivity will offer opportunities for enhanced molecular diagnostics and image-guided biomedical applications.

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Figure 1: Schematic of the dual-stimuli signal-amplification process of the probe and its photophysical properties.
Figure 2: Probe responses to acidity and oxygenation in cell culture, and immunofluorescence staining of tumour sections.
Figure 3: Optical imaging of mice bearing tumour xenografts.
Figure 4: Detection of metastatic liver lesions and orthotopic hepatocellular carcinoma.
Figure 5: Probe responses to drug-induced OCR and ECAR changes.

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Acknowledgements

This work was supported by the Natural Science Foundation of China (grant nos. 51690153, 21474045 and 51422303), the Specialized Research Fund for the Doctoral Program of Higher Education, and the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), Ministry of Education of China.

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Authors and Affiliations

  1. and Department of Polymer Science and Engineering, MOE Key Laboratory of High Performance Polymer Materials and Technology, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.

    Xianchuang Zheng, Wei Wu & Xiqun Jiang

  2. Department of Radiology and Imaging Sciences, Emory University, Atlanta, 30329, Georgia, USA.

    Hui Mao

  3. Institute of Materials Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, 210093, China.

    Da Huo

  4. Department of Oncology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China.

    Baorui Liu

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  1. Xianchuang Zheng
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Contributions

X.Z., H.M. and X.J. conceived and designed the research. X.Z., D.H. and W.W. performed the experiments. X.Z., H.M., X.J. and B.L. analysed the data and wrote the manuscript. X.J. supervised the project.

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Correspondence to Xiqun Jiang.

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Zheng, X., Mao, H., Huo, D. et al. Successively activatable ultrasensitive probe for imaging tumour acidity and hypoxia. Nat Biomed Eng 1, 0057 (2017). https://doi.org/10.1038/s41551-017-0057

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