Intravital Imaging of Human Prostate Cancer Using Viral Nanoparticles Targeted to Gastrin-Releasing Peptide Receptors

Authors

  • Nicole F. Steinmetz,

    1. Department of Cell Biology, Center of Integrative Molecular Biosciences, The Scripps Research Institute, North Torrey Pines Rd., La Jolla, CA 92037, USA
    Current affiliation:
    1. Current address: Department of Biomedical Engineering, Case Center for Imaging Research, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA
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    • These authors contributed equally to this paper.

  • Amber L. Ablack,

    1. Translational Prostate Cancer Research Group, London Regional Cancer Program, Room A4-823, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada, Phone: 1–519-685–8600 x57194, Fax: 1–866-426–6697
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    • These authors contributed equally to this paper.

  • Jennifer L. Hickey,

    1. Department of Chemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
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    • These authors contributed equally to this paper.

  • Jailal Ablack,

    1. Department of Oncology, London Regional Cancer Program, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada
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  • Bhavik Manocha,

    1. Translational Prostate Cancer Research Group, London Regional Cancer Program, Room A4-823, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada, Phone: 1–519-685–8600 x57194, Fax: 1–866-426–6697
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  • Joe S. Mymryk,

    1. Department of Oncology, London Regional Cancer Program, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada
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  • Leonard G. Luyt,

    1. Department of Chemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada
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  • John D. Lewis

    Corresponding author
    1. Translational Prostate Cancer Research Group, London Regional Cancer Program, Room A4-823, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada, Phone: 1–519-685–8600 x57194, Fax: 1–866-426–6697
    • Translational Prostate Cancer Research Group, London Regional Cancer Program, Room A4-823, 790 Commissioners Rd. E., London, Ontario N6A 4L6, Canada, Phone: 1–519-685–8600 x57194, Fax: 1–866-426–6697.
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Abstract

Multivalent nanoparticles have several key advantages in terms of solubility, binding avidity, and uptake, making them particularly well suited to molecular imaging applications. Herein is reported the stepwise synthesis and characterization of NIR viral nanoparticles targeted to gastrin-releasing peptide receptors that are over-expressed in human prostate cancers. The pan-bombesin analogue, [β-Ala11, Phe13, Nle14]bombesin-(7–14), is conjugated to cowpea mosaic virus particles functionalized with an NIR dye (Alexa Fluor 647) and polyethylene glycol (PEG) using the copper(I)-catalyzed azide-alkyne cycloaddition reaction. Targeting and uptake in human PC-3 prostate cells is demonstrated in vitro. Tumor homing is observed using human prostate tumor xenografts on the chicken chorioallantoic membrane model using intravital imaging. Further development of this viral nanoparticle platform may open the door to potential clinical noninvasive molecular imaging strategies.

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