High efficiency of 5-aminolevulinate-photodynamic treatment using UVA irradiation

Photodynamic therapy (PDT) is being used clinically for the treatment of sk in cancers. One concept of delivering the employed photosensitizer directly to target cells is to stimulate cellular synthesis of sensitizers such as porphyrins. ALA (5-aminolevulinate) is applied as a precursor of porphyrins which then serve as endogenous photosensitizers, Upon irradiation, reactiv e oxygen species, predominantly singlet oxygen, are generated, leading to c ell death. ALA-PDT using red light (550-750 nm) is known to lead to the act ivation of stress kinases, such as c-Jun-N-terminal kinase and p38. These k inases are also activated by UVA (320-400 nm), whose biological effects are mediated in part by singlet oxygen. In the present study, the efficiency o f a combination of both treatment strategies, ALA-PDT and UVA, in cytotoxic ity and activation of stress kinases was investigated taking human skin fib roblasts as a model, Compared with the commonly used ALA-PDT with red light (LD50 = 13.5 J/cm(2)), UVA-ALA-PDT was 40-fold more potent in killing cult ured human skin fibroblasts (LD50 = 0.35 J/cm(2)) and still 10-fold more po tent than ALA-PDT with green light (LD50 4.5 J/cm(2)). Its toxicity relied on the formation of singlet oxygen, as was shown employing modulators of si nglet oxygen lifetime, In line with these data, strong activation of the st ress kinase p38 was obtained in ALA-pretreated cells irradiated with UVA at doses two orders of magnitude lower than necessary for a comparable activa tion of p38 by UVA in control cells, Taken together, these data suggest UVA -ALA-PDT as a potentially interesting new approach in the photodynamic trea tment of skin diseases.