Aluminium phthalocyanines-induced photolysis of human vascular wall cells in culture and the effect of fluoride on photodynamic action.
BACKGROUND
Phthalocyanines, second-generation photosensitizers with several attractive properties for use in photodynamic therapy, have been shown to accumulate in malignant lesions and atherosclerotic plaques. After exposure of phthalocyanines-loaded tissues to visible light, the targeted cells become injured and eventually die. In vitro, when fluoride is added before exposure to the light, it can protect some cell types against photodynamic action sensitized by chloroaluminium phthalocyanine (AIPc) and its derivatives.


METHODS
The effect of 50 mumol/l chloroaluminium phthalocyanine tetrasulfonate (AIPcS4) and 5 mumol/l AIPc, with and without the addition of 5 mumol/l NaF, on the viability of cultured human endothelial cells (HuEC), human smooth muscle cells (HuSMC), and skin fibroblasts (HuSF) was examined. A 150 W quartz halogen light bulb equipped with a cut-off filter (lambda > 605 nm) was used to activate the phthalocyanines. Cell viability was examined 24 h after irradiation by staining of the cells with fluorescein diacetate/ethidiumbromide and by counting the number of attached cells with a cell counter.


RESULTS
In the case of AIPc, the viability of all cell types tested was reduced, in a dose-dependent manner, to about 50% of that of the corresponding controls for a maximum irradiation time of 600 s. When we used AIPcS4, both HuEC and HuSF were considerably less sensitive than HuSMC. The addition of fluoride to AIPc-loaded cells before exposure to light protected HuEC and HuSF, but not HuSMC. In the case of AIPcS4, with and without fluoride, only HuSMC were sensitive.


CONCLUSIONS
The addition of fluoride to AIPc or the use of AIPcS4 without fluoride could be a valuable approach, selectively destroying HuSMC without affecting HuEC and HuSF, for the reduction of restenosis rates after recanalization of stenosed or occluded arteries. Moreover, because neither type of phthalocyanines causes cutaneous phototoxicity, these second-generation photosensitizers seem to be best suited to the photodynamic treatment of atherosclerosis.
Dartsch
P C
PC
Institute of Physiology (I), University of Tübingen, Germany.
Wunderlich
K
K
Ben-Hur
E
E
D001161:Arteriosclerosis / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010778:Photochemotherapy / Q000379:methods*; D010782:Photolysis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012867:Skin / Q000166:cytology
D007211:Indoles; D054833:Isoindoles; D011838:Radiation-Sensitizing Agents; D005459:Fluorides; C013647:phthalocyanine