Evaluation of porphyrin characteristics required for photodynamic therapy.
The cytotoxicity (in the dark), phototoxicity (red light) and subcellular localization (using confocal laser scanning microscopy) were determined for 15 porphyrins (1-15) in C6 glioma cells. The partition coefficient in 2-octanol was also determined for each porphyrin at pH 7.4. The cytotoxicity increased with pi (log of partition coefficient) up to pi values of +2. The 7 porphyrins with cationic side chains exhibited a classical parabolic correlation between phototoxicity and pi, with maximal activity at a pi value of approximately 1.0. There was also a significant correlation between subcellular localization and degree of phototoxicity, with the three most photosensitive porphyrins all possessing cationic side chains, and all three localizing in mitochondria.
Woodburn
K W
KW
Biochemistry Department, La Trobe University, Bundoora, Victoria, Australia.
Vardaxis
N J
NJ
Hill
J S
JS
Kaye
A H
AH
Reiss
J A
JA
Phillips
D R
DR
D002470:Cell Survival / Q000187:drug effects; D010777:Photochemistry; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D011166:Porphyrins