Cellular uptake and photocytotoxicity of glycoconjugated porphyrins in HeLa cells.
Thirty-two glycoconjugated porphyrins were synthesized by a modification of Lindsey method in the presence of Zn(OAc)(2).2H(2)O as a template. The Zn(2+) ion template strategy improved the yield about three-fold in the case of meta-substituted tetraphenylporphyrins. In addition, free-base porphyrins were obtained almost quantitatively by demetalation with 4 M HCl. Sixteen deacetylated glycoconjugated porphyrins were tested as candidate photodynamic therapy (PDT) drugs using HeLa cells. Most of the deacetylated glycoconjugated porphyrins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS), and 5,10,15,20-tetrakis[4-(beta-D-arabinopyranosyloxy)phenyl]porphyrin (p-5d) in particular showed 18.5-fold higher uptake than TPPS. The photocytotoxicity of 5,10,15,20-tetrakis[4-(beta-D-glucopyranosyloxy)phenyl]porphyrin (p-5a), p-5d and TPPS was examined with HeLa cells, using a light dose of 16 J/cm(2). These photosensitizers had no cytotoxicity in the dark, but their photocytotoxicity increased in the order of TPPS < p-5a < p-5d. These results suggest p-5d is a good candidate for a PDT drug.
Hirohara
Shiho
S
Division of Material Science, Graduate School of Human Culture, Nara Women's University, Nara 630-8560, Japan.
Obata
Makoto
M
Saito
Atsuhiro
A
Ogata
Shin-ichi
S
Ohtsuki
Chikara
C
Higashida
Suguru
S
Ogura
Shun-ichiro
S
Okura
Ichiro
I
Sugai
Yuko
Y
Mikata
Yuji
Y
Tanihara
Masao
M
Yano
Shigenobu
S
D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000097:blood / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D011166:Porphyrins / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
D017319:Photosensitizing Agents; D011166:Porphyrins