Cellular uptake and photocytotoxicity of glycoconjugated chlorins in HeLa cells

Eight 5,10,15,20-tetrakis[3- or 4-(β-d-glycopyranosyloxy)phenyl]chlorins were synthesized by means of the Whitlock method with diimide reduction and purified by reversed-phase thin layer chromatography (RP-TLC). All compounds were characterized by 1H NMR spectroscopy, electron-spray ionization time-of-flight mass spectrometry (ESI-TOF MS), and UV-Vis spectroscopy. ESI-TOF MS could detect the 2H difference in molecular weight between a glycoconjugated chlorin and its corresponding porphyrin (i.e., 5,10,15,20-tetrakis[3- or 4-(β-d-glycopyranosyloxy)phenyl]porphyrin). The cellular uptake of the eight chlorins was evaluated in HeLa cells. All glycoconjugated chlorins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS), and 5,10,15,20-tetrakis[3-(β-d-xylopyranosyloxy)phenyl]chlorin showed 50-fold higher uptake than TPPS. The photocytotoxicity of 5,10,15,20-tetrakis[3-(β-d-glucopyranosyloxy)phenyl]chlorin, 5,10,15,20-tetrakis[3-(β-d-xylopyranosyloxy)phenyl]chlorin and TPPS towards HeLa cells was examined at the concentration of 2 × 10−7 M (mol/dm3). These photosensitizers had no cytotoxicity in the dark, but their photocytotoxicity decreased in the order of 5,10,15,20-tetrakis[3-(β-d-glucopyranosyloxy)phenyl]chlorin > 5,10,15,20-tetrakis[3-(β-d-xylopyranosyloxy)phenyl]chlorin > TPPS. The results indicate that the photocytotoxicity is not related simply to cellular uptake.