Lipophilic pro-oligonucleotides are rapidly and efficiently internalized in HeLa cells

Model t-Bu-SATE pro-dodecathymidines labeled with fluorescein and exhibitin g various lipophilicities were evaluated for their uptake by cells in cultu re. Pro-oligonucleotides with appropriate lipophilicity were found to perme ate across the HeLa cell membrane much more extensively than the control ph osphorothioate oligo or than the hydrophilic prooligos. Fluorescence patter ns of internalization were consistent with a diffusion mechanism resulting in the appearance of a uniform cytoplasmic distribution and nuclear accumul ation, as confirmed by confocal microscopy.