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Research ArticleArticle

In Vivo Labeling of Brain Capillary Endothelial Cells after Intravenous Injection of Monoclonal Antibodies Targeting the Transferrin Receptor

Sarah Paris-Robidas, Vincent Emond, Cyntia Tremblay, Denis Soulet and Frédéric Calon
Molecular Pharmacology July 2011, 80 (1) 32-39; DOI: https://doi.org/10.1124/mol.111.071027
Sarah Paris-Robidas
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Vincent Emond
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Cyntia Tremblay
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Denis Soulet
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Frédéric Calon
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Abstract

The development of vectors for drug delivery to the central nervous system remains a major pharmaceutical challenge. Here, we have characterized the brain distribution of two monoclonal antibodies (MAbs) targeting the mouse transferrin receptor (TfR) (clones Ri7 and 8D3) compared with control IgGs after intravenous injection into mice. MAbs were fluorolabeled with either Alexa Fluor (AF) dyes 647 or 750. Intravenous injection of Ri7 or 8D3 MAb coupled with AF750 led to higher fluorescence emission in brain homogenates compared with control IgGs, indicating retention in the brain. Fluorescence microscopy analysis revealed that AF647-Ri7 signal was confined to brain cerebrovasculature, colocalizing with an antibody against collagen IV, a marker of basal lamina. Confocal microscopy analysis confirmed the delivery of injected Ri7 MAb into brain endothelial cells using the pericyte marker anti-α-smooth muscle actin, the endothelial marker CD31, and the collagen IV antibody. No evidence of colocalization was detected with neurons or astrocytes identified using antibodies specific for neuronal nuclei or glial fibrillary acidic protein, respectively. Our data show that anti-TfR vectors injected intravenously readily accumulate into brain capillary endothelial cells, thus displaying strong drug-targeting potential.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported by the Canadian Institutes of Health Research (CIHR) [Grant FC-MOP84251]; the Alzheimer Society Canada [Grant FC-ASC 0516)]; the Canada Foundation for Innovation [Grant 10307]; and a New Investigator Award from the Clinical Research Initiative and the CIHR Institute of Aging [Grant CAN76833].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.111.071027.

  • ABBREVIATIONS:

    BCEC
    brain capillary endothelial cell
    α-SMA
    α-smooth muscle actin
    AF
    Alexa Fluor
    BBB
    blood-brain barrier
    CNS
    central nervous system
    DAPI
    4′,6-diamidino-2-phenylindole
    GFAP
    glial fibrillary acidic protein
    MAb
    monoclonal antibody
    MMCO
    molecular mass cutoff
    NeuN
    neuronal nuclei
    PBS
    phosphate-buffered saline
    PFA
    paraformaldehyde
    Ri7
    cell line Ri7217.1.4
    TBS
    Tris-buffered saline
    TfR
    transferrin receptor
    RT
    room temperature.

  • Received January 12, 2011.
  • Accepted March 31, 2011.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 80 (1)
Molecular Pharmacology
Vol. 80, Issue 1
1 Jul 2011
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Research ArticleArticle

In Vivo Labeling of Brain Capillary Endothelial Cells after Intravenous Injection of Monoclonal Antibodies Targeting the Transferrin Receptor

Sarah Paris-Robidas, Vincent Emond, Cyntia Tremblay, Denis Soulet and Frédéric Calon
Molecular Pharmacology July 1, 2011, 80 (1) 32-39; DOI: https://doi.org/10.1124/mol.111.071027

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Research ArticleArticle

In Vivo Labeling of Brain Capillary Endothelial Cells after Intravenous Injection of Monoclonal Antibodies Targeting the Transferrin Receptor

Sarah Paris-Robidas, Vincent Emond, Cyntia Tremblay, Denis Soulet and Frédéric Calon
Molecular Pharmacology July 1, 2011, 80 (1) 32-39; DOI: https://doi.org/10.1124/mol.111.071027
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