Synthesis and in vitro photodynamic activities of water-soluble fluorinated tetrapyridylporphyrins as tumor photosensitizers.
A series of water-soluble fluorinated cationic porphyrins were designed, synthesized, and characterized. In vitro photocytotoxicity of these compounds was evaluated by MTT assay on HeLa cells. Their photocytotoxicity was dependent on the positions of the cations and the fluorines in the pyridine ring, and 5,10,15,20-tetrakis-(N-methyl-2-fluoro-pyridin-3-yl)-porphyrin (8) showed the most potent photo-induced cytotoxicity without photobleaching. PDT-induced ROS inside HeLa cells was measured with flow cytometry using ROS-sensitive fluorometric probe, 2,7-dichlorofluororescin (DCF), which revealed high correlations of ROS with cellular cytotoxicity. FACS analysis shows that PDT with porphyrin 8 induced apoptosis in HeLa cells. In summary, efficient generation of ROS, biological effectiveness, and good photostability of porphyrin 8 indicate its potential application in photodynamic therapy (PDT) in the near future.
Ko
Yoon-Joo
YJ
Department of Chemistry, Seoul National University, Seoul 151-747, South Korea.
Yun
Kyung-Jin
KJ
Kang
Min-Seok
MS
Park
Jongmin
J
Lee
Kyung-Tae
KT
Park
Seung Bum
SB
Shin
Jung-Hyu
JH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005461:Fluorine / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000627:therapeutic use; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; D005461:Fluorine