Photosensitization and mechanism of cytotoxicity induced by the use of ALAderivatives in photodynamic therapy

Citation
A. Casas et al., Photosensitization and mechanism of cytotoxicity induced by the use of ALAderivatives in photodynamic therapy, BR J CANC, 85(2), 2001, pp. 279-284
Citations number
35
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
00070920 → ACNP
Volume
85
Issue
2
Year of publication
2001
Pages
279 - 284
Database
ISI
SICI code
0007-0920(20010720)85:2<279:PAMOCI>2.0.ZU;2-J
Abstract
The use of more lipophilic derivatives of 5-aminolevulinic acid (ALA) is ex pected to have better diffusing properties, and after conversion into the p arent ALA, to reach a higher protoporphyrin IX (PPIX) formation rate, thus improving the efficacy of topical photodynamic therapy (PDT). Here we have analysed the behaviour of 3 ALA derivatives (ALA methyl-ester, hexyl ester and a 2-sided derivative) regarding PPIX formation, efficiency in photosens itizing cells and mechanism of cellular death. The maximum amount of porphy rins synthesized from 0.6 mM ALA was 47 +/- 8 ng/10(5) cells. The same amou nt was formed by a concentration 60-fold lower of hexyl-ALA and 2-fold high er of methyl-ALA. The 2-sided derivative failed to produce PPIX accumulatio n. Applying a 0.6 J cm(-2) light dose, cell viability decreased to 50%. Wit h the 1.5 J cm(-2) light dose, less than 20% of the cells survive, and high er light doses produced nearly total cell killing. Comparing the PPIX produ ction and the induced phototoxicity, the more the amount of porphyrins, the greater the cellular killing, and PPIX formed from either ALA or ALA-ester s equally sensitize the cells to photo inactivation. ALA-PDT treated cells exhibited features of apoptosis, independently on the pro-photosensitizer e mployed. ALA-PDT can be improved with the use of ALA derivatives, reducing the amount of ALA necessary to induce efficient photosensitization. (C) 200 1 Cancer Research Campaign.