Assessment of the cytotoxicity of the photosensitizing drug BPD verteporfin using human vascular smooth muscle cells in culture.
Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the drugs cytotoxic. However, skin photosensitivity which persists for many weeks is a significant side effect. We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD verteporfin (Quadra Logic Technologies), which does not have this deleterious side effect. Vascular smooth muscle cells (VSMC) from normal human mammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The sensitivity to BPD with and without light was assessed by measuring viability after treatment. The lethal dose of drug for 50% viability loss (LD50) for BPD with light was approximately 12.5 ng/ml for mammary artery, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC from all patient sources, although differing significantly in growth rate, had a survival of 44 +/- 6% (n = 12) at the same concentration of BPD used for the mammary artery SMC (p = NS). Our results established the LD50 for BPD using human arterial sources of SMC and showed that the growth rates of the cells did not affect the cytotoxicity of the drug.
Labow
R S
RS
University of Ottawa Heart Institute, Ottawa Civic Hospital, Canada.
Higginson
L A
LA
Irvine
J
J
Keaney
M
M
Masters
R G
RG
Marquis
J F
JF
Meek
E
E
Mussivand
T
T
Walley
V M
VM
Logan
P
P
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007928:Lethal Dose 50; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D011166:Porphyrins / Q000494:pharmacology*; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin