Cellular uptake and photocytotoxicity of glycoconjugated chlorins in HeLa cells.
Eight 5,10,15,20-tetrakis[3- or 4-(beta-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 (1)H 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-(beta-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-(beta-D-xylopyranosyloxy)phenyl]chlorin showed 50-fold higher uptake than TPPS. The photocytotoxicity of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin, 5,10,15,20-tetrakis[3-(beta-D-xylopyranosyloxy)phenyl]chlorin and TPPS towards HeLa cells was examined at the concentration of 2x10(-7) M (mol/dm(3)). These photosensitizers had no cytotoxicity in the dark, but their photocytotoxicity decreased in the order of 5,10,15,20-tetrakis[3-(beta-D-glucopyranosyloxy)phenyl]chlorin>5,10,15,20-tetrakis[3-(beta-D-xylopyranosyloxy)phenyl]chlorin>TPPS. The results indicate that the photocytotoxicity is not related simply to cellular uptake.
Hirohara
Shiho
S
Division of Material Science, Graduate School of Human Culture, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan.
Obata
Makoto
M
Ogata
Shin-ichi
S
Ohtsuki
Chikara
C
Higashida
Suguru
S
Ogura
Shun-ichiro
S
Okura
Ichiro
I
Takenaka
Makiko
M
Ono
Hiroshi
H
Sugai
Yuko
Y
Mikata
Yuji
Y
Tanihara
Masao
M
Yano
Shigenobu
S
D001692:Biological Transport; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010777:Photochemistry; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D013057:Spectrum Analysis
D011166:Porphyrins; C006969:chlorin