Photosensitization of L1210 leukaemic cells by argon laser irradiation after incubation with haematoporphyrin derivative and rhodamine 123.
The selectivity and efficacy of photodynamic therapy (PDT) may be improved by the combined use of photosensitizers in a similar manner to the combined use of drugs in cancer chemotherapy. Two photosensitizers (haematoporphyrin derivative (HPD) and rhodamine 123 (Rh-123) were analysed which can be irradiated at the same wavelength (514 nm), are preferentially taken up by tumour tissue and are not specific for the same target (membrane for HPD, mitochondria for Rh-123). The analysis of the phototoxic effects in surviving fractions showed a dependence on dose for both products and a dependence on incubation time for HPD but not Rh-123. The lethal dose for 50% cell death (LD50) for HPD increased from 25 to 56 J cm-2 when the HPD dose was reduced from 2.5 to 1 micrograms ml-1 for the same incubation time. When the incubation time was increased from 15 to 45 min, the surviving fraction decreased by 37% and 17% for doses of 1 and 2.5 micrograms ml-1 respectively. For low doses (0.5 and 1 microgram ml-1), the toxicity of the two photosensitizers added simultaneously was weaker than for Rh-123 alone, whereas for high doses (2.5 micrograms ml-1) the surviving fraction was less than that obtained with Rh-123 alone. These results were compared with the light energy absorbed, the quantum yield of singlet oxygen and Rh-123 uptake as determined by flow cytometry analysis.
Foultier
M T
MT
Département Laser, Faculté de Pharmacie, Nantes, France.
Patrice
T
T
Tanielian
C
C
Wolff
C
C
Yactayo
S
S
Berrada
A
A
Combre
A
A
D000818:Animals; D001128:Argon; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D007700:Kinetics; D007834:Lasers; D007939:Leukemia L1210 / Q000473:pathology*; D008027:Light; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D010777:Photochemistry; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D026082:Singlet Oxygen; D014407:Tumor Cells, Cultured
D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D012235:Rhodamines; D026082:Singlet Oxygen; D020112:Rhodamine 123; D001128:Argon; D017324:Hematoporphyrin Derivative; D010100:Oxygen