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Switching the Targeting Pathways of a Therapeutic Antibody by Nanodesign

Authors

  • Dr. Sanjib Bhattacharyya,

    1. Department of Biochemistry and Molecular Biology, Guggenheim 1311B, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (USA)
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  • Dr. Raman Deep Singh,

    1. Department of Biochemistry and Molecular Biology, Guggenheim 1311B, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (USA)
    2. Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN 55905 (USA)
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  • Dr. Richard Pagano,

    1. Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN 55905 (USA)
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    • Deceased

  • Dr. J. David Robertson,

    1. Department of Chemistry and University of Missouri Research Reactor, University of Missouri, Columbia, MO 65211 (USA)
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  • Dr. Resham Bhattacharya,

    1. Department of Biochemistry and Molecular Biology, Guggenheim 1311B, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (USA)
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  • Dr. Priyabrata Mukherjee

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Guggenheim 1311B, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (USA)
    2. Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 (USA)
    3. Cancer Center, College of Medicine, Mayo Clinic, Rochester, MN 55905 (USA)
    • Department of Biochemistry and Molecular Biology, Guggenheim 1311B, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (USA)
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  • This work was supported by the National Institutes of Health (NIH) grants CA135011, and CA136494 to P.M. We are thankful to John Charlesworth and Cindy B. Uhl for helping with TEM image analysis. We gratefully acknowledge James E. Tarara for helping with confocal image analysis. We also acknowledge Prof. Cord Brakebusch and Mark McNiven for providing the Cdc42-null cells and the EGFR-GFP construct, respectively.

Abstract

original image

Goldener Pfad: Die Endozytosemechanismen von Cetuximab (C225) und dessen Nanokonjugaten wurden in einer Pankreaskrebszelllinie aufgeklärt. Mit Goldnanopartikeln als Trägersystem ließ sich der Reaktionspfad für die Endozytose von einem Dyn-2-abhängigen kaveolären Mechanismus zu einer Cdc42-abhängigen Pinozytose/Phagozytose schalten. Die gezielte Einstellung von Endozytosemechanismen könnte es ermöglichen, in spezifische intrazelluläre Reaktionspfade einzugreifen.

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