On the correlation between hydrophobicity, liposome binding and cellular uptake of porphyrin sensitizers

Shimshon Ben-Dror, Irena Bronshtein, Arno Wiehe, Beate Rôder, Mathias O. Senge, Benjamin Ehrenberg

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


A crucial factor in choosing a porphyrin or analogous photosensitizer for photodynamic therapy (PDT) is its ability to incorporate into the cells. For hydrophobic compounds that partition passively into the cytoplasmic membrane, a partition coefficient between an organic solvent and water, P, is one factor that could be used to predict the molecule's ability to diffuse into biomembranes. We synthesized several porphyrins, modified with two, three or four meso-substituents and studied their spectroscopic and photophysical properties. The octanol-water partitioning coefficients, log P, were calculated as a parameter for hydrophobicity. We found these porphyrins to be very hydrophobic, with log P values in the range of 8.9-11.8. These were correlated with the binding constants of these porphyrins into liposomes, Kb, as well as to their uptake by cells. The correlation between the estimated log P and Kb is nearly linear but negative, indicating, apparently, that there is lesser binding to liposomes with increased hydrophobicity. On the other hand, all of the studied porphyrins are taken up by cells, but there is no clear correlation between cellular uptake and the log P or Kb. Lipinski's pharmacological "rule of 5" predicts poor permeation of drugs into cells when log P is greater than five. This may be relevant for diffusional binding to liposomes, where aqueous aggregation can interfere strongly with cellular uptake. In such extreme conditions, neither liposome binding nor other rules seem to predict porphyrin behavior in vitro.

Original languageEnglish
Pages (from-to)695-701
Number of pages7
JournalPhotochemistry and Photobiology
Issue number3
StatePublished - May 2006


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