Multifunctional nanobeacon for imaging Thomsen-Friedenreich antigen-associated colorectal cancer

Authors

  • Hironori Kumagai,

    1. Institute of Imaging Science, Vanderbilt University, Nashville, TN
    2. Advanced Materials Laboratory, ADEKA Corp., Tokyo, Japan
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  • Wellington Pham,

    Corresponding author
    1. Institute of Imaging Science, Vanderbilt University, Nashville, TN
    2. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN
    3. Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN
    4. Vanderbilt Institute of Chemical Biology, Nashville, TN
    5. Neuroscience, Vanderbilt University, Nashville, TN
    • Institute of Imaging Science, Vanderbilt University, 1161, 21st Avenue South, Nashville, TN 37232, USA
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    • Tel.: 615-936-7621, Fax: +1-615-322-0734, Shinji Sakuma, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan, Tel: +81-72-866-3124, Fax: +81-72-866-3126.

  • Makoto Kataoka,

    1. Institute of Imaging Science, Vanderbilt University, Nashville, TN
    2. Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan
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  • Ken-Ichiro Hiwatari,

    1. Advanced Materials Laboratory, ADEKA Corp., Tokyo, Japan
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  • James McBride,

    1. Department of Chemistry, Vanderbilt University, Nashville, TN
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  • Kevin J. Wilson,

    1. Institute of Imaging Science, Vanderbilt University, Nashville, TN
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  • Hiroyuki Tachikawa,

    1. Advanced Materials Laboratory, ADEKA Corp., Tokyo, Japan
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  • Ryoji Kimura,

    1. Advanced Materials Laboratory, ADEKA Corp., Tokyo, Japan
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  • Kunio Nakamura,

    1. Advanced Materials Laboratory, ADEKA Corp., Tokyo, Japan
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  • Eric H. Liu,

    1. Department of Surgery, Division of Surgical Oncology and Endocrinology, Vanderbilt University School of Medicine, Nashville, TN
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  • John C. Gore,

    1. Institute of Imaging Science, Vanderbilt University, Nashville, TN
    2. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN
    3. Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN
    4. Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN
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  • Shinji Sakuma

    Corresponding author
    1. Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan
    • Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan
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Abstract

This research aimed to validate the specificity of the newly developed nanobeacon for imaging the Thomsen-Friedenreich (TF) antigen, a potential biomarker of colorectal cancer. The imaging agent is comprised of a submicron-sized polystyrene nanosphere encapsulated with a Coumarin 6 dye. The surface of the nanosphere was modified with peanut agglutinin (PNA) and poly(N-vinylacetamide (PNVA) moieties. The former binds to Gal-β(1-3)GalNAc with high affinity while the latter enhances the specificity of PNA for the carbohydrates. The specificity of the nanobeacon was evaluated in human colorectal cancer cells and specimens, and the data were compared with immunohistochemical staining and flow cytometric analysis. Additionally, distribution of the nanobeacon in vivo was assessed using an “intestinal loop” mouse model. Quantitative analysis of the data indicated that approximately 2 μg of PNA were detected for each milligram of the nanobeacon. The nanobeacon specifically reported colorectal tumors by recognizing the tumor-specific antigen through the surface-immobilized PNA. Removal of TF from human colorectal cancer cells and tissues resulted in a loss of fluorescence signal, which suggests the specificity of the probe. Most importantly, the probe was not absorbed systematically in the large intestine upon topical application. As a result, no registered toxicity was associated with the probe. These data demonstrate the potential use of this novel nanobeacon for imaging the TF antigen as a biomarker for the early detection and prediction of the progression of colorectal cancer at the molecular level.

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