Fluorinated Cells for Cancer Therapy and Diagnostics
In collaboration with Prof. Krishna Kumar’s laboratory at Tufts University, we are endeavoring to decorate the glycocalyx on the surface of cells in vivo with fluorinated carbohydrates to alter their physical and biological properties. Since fluorinated surfaces are generally both hydrophobic and lipophobic, they typically exhibit reduced intermolecular interactions with non-fluorinated surfaces (e.g. Teflon®). Since tumor metastasis requires interaction of the tumor cell glycocalyx with proteins in the extracellular matrix (ECM) and on other cells, we expect tumor cells decorated with fluorinated groups to exhibit reduced adhesion to these molecules and perhaps diminished propensity for metastasis.
Our strategy for fluorinating cells is based on a sialic acid glycoengineering approach pioneered by the Reutter1 and Bertozzi2 laboratories. This approach makes use of the promiscuity of the cell-surface sialoside bio-synthesis pathway and involves treating the cells with an appropriately modified biosynthetic precursor. This method has been used to modify cell surface sialosides in living animals without apparent toxicity.3-6
In our work,7-9 cells modified with fluorinated sialic acids indeed show reduced adhesion to ECM proteins. We are currently engaged in a study of the molecular mechanism10,11 of this effect, the applications for anti-metastasis therapy, and, because of the increase in cancer cell sialylation and the paucity of fluorine in soft tissues, the possibility of using this method as a cancer diagnostic method.
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in press. doi: 10.1093/glycob/cwv019 [html]
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