Synthesis, cellular uptake of, and cell photosensitization by a porphyrin bearing a quinoline group.
A tetraphenyl porphine linked to a 7-chloroquinoline (5,10,15,20-tetraphenyl-1-3-[4-(4-aminobutyl)7-chloroquinoline] propioamidoporphine, TPPQ) was synthesized and examined as a potential photosensitizer for photodynamic therapy (PDT) of proliferative diseases. With respect to haematoporphyrin, TPPQ is a good in vitro photodynamic sensitizer producing singlet oxygen in 1% Triton X100 solutions. As with other hydrophobic porphyrins used in PDT, blood lipoproteins strongly bind TPPQ. Thus one low density lipoprotein (LDL) can incorporate 25 TPPQ molecules and 17 TPPQ molecules are taken up by one high density lipoprotein (HDL). Cell delivery of TPPQ using HDL or human serum albumin (HSA) as carrier is rather weak. However, an efficient TPPQ delivery to human skin fibroblasts is observed, partly aided by receptor-mediated endocytosis of LDL. Fluorescence spectroscopy shows that the cellular localization of TPPQ is both carrier and time dependent. During its delivery with LDL, TPPQ does not significantly impair the endocytosis of LDL-receptor complexes. After delivery with LDL, TPPQ is as efficient as other haematoporphyrin derivatives used in the PDT of cancers in photosensitizing human skin fibroblasts.
Morlière
P
P
Laboratoire de Dermatologie, INSERM U.312, Hôpital Henri Mondor, Creteil, France.
Momenteau
M
M
Candide
C
C
Simonin
V
V
Santus
R
R
Mazière
J C
JC
Dubertret
L
L
Goldstein
S
S
Hüppe
G
G
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004705:Endocytosis; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D010778:Photochemotherapy; D011166:Porphyrins / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D011973:Receptors, LDL / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013050:Spectrometry, Fluorescence
D000634:Aminoquinolines; D001798:Blood Proteins; D007202:Indicators and Reagents; D011166:Porphyrins; D011973:Receptors, LDL; C064271:5,10,15,20-tetraphenyl-1-3-(4-(4-aminobutyl)-7-chloroquinoline)propioamidoporphine