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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Toward a cancer therapy with boron-rich oligomeric phosphate diesters that target the cell nucleus.

The viability of boron neutron capture therapy depends on the development of tumor-targeting agents that contain large numbers of boron-10 (10B) atoms and are readily taken up by cells. Here we report on the selective uptake of homogeneous fluorescein-labeled nido-carboranyl oligomeric phosphate diesters (nido-OPDs) by the cell nucleus and their long-term retention after their delivery into the cytoplasm of TC7 cells by microinjection. All nido-OPDs accumulated in the cell nucleus within 2 h after microinjection. However, nido-OPDs in which the carborane cage was located on a side chain attached to the oligomeric backbone were redistributed between both the cytoplasm and nucleus after 24 h of incubation, whereas nido-OPDs in which the carborane cage was located along the oligomeric backbone remained primarily in the nucleus. Furthermore, cell-free incubation of digitonin-permeabilized TC7 cells with the nido-OPDs resulted in nuclear accumulation of the compounds, thus corroborating the microinjection studies. Our observation of fluorescence primarily located in the cell nucleus indicates that nuclear-specific uptake of sufficient amounts of 10B for effective boron neutron capture therapy ( approximately 10(8)-10(9) 10B atoms/tumor cell) via nido-OPDs is achievable.[1]

References

  1. Toward a cancer therapy with boron-rich oligomeric phosphate diesters that target the cell nucleus. Nakanishi, A., Guan, L., Kane, R.R., Kasamatsu, H., Hawthorne, M.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
 
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