Zn(II)-phthalocyanines as phototherapeutic agents for cutaneous diseases. Photosensitization of fibroblasts and keratinocytes.
Two tetrasubstituted (RLP024 and RLP040) and one monosubstituted (MRLP101) Zn-phthalocyanines were readily accumulated by three skin-derived cell lines (HT-1080 transformed human fibroblasts, 3T3 mouse embryo fibroblasts and HaCaT human keratinocytes) upon 1 h-incubation with 0.5-5 microM phthalocyanine concentrations. The affinity was markedly larger for the tetra- as compared with the mono-substituted phthalocyanine, even though smaller phthalocyanine amounts were generally recovered from keratinocytes. As a consequence, the two tetra-substituted phthalocyanines exhibited a higher phototoxicity against all the three cell lines. Typically, the cell survival decreased by at least 80% after 1 min irradiation with 600-700 nm light at a fluence-rate of 50 mW/cm2 in the presence of 5 microM phthalocyanine. Fluorescence microscopy and caspase-3 activation studies indicate that cell death of fibroblasts largely occurred by a random-necrotic process while the keratinocytes underwent cell death predominantly via apoptosis in spite of a very similar pattern of subcellular distribution of the phthalocyanines.
Fabris
Clara
C
Molteni Farmaceutici, S.S. 67 Loc.Granatieri, 50018 Scandicci, Firenze, Italy.
Soncin
Marina
M
Miotto
Giovanni
G
Fantetti
Lia
L
Chiti
Giacomo
G
Dei
Donata
D
Roncucci
Gabrio
G
Jori
Giulio
G
D016475:3T3 Cells; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D054833:Isoindoles; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000627:therapeutic use*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012871:Skin Diseases / Q000532:radiotherapy*; D013329:Structure-Activity Relationship; D017967:Zinc Compounds
D001562:Benzimidazoles; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C017807:bisbenzimide ethoxide trihydrochloride