Spectroscopic properties and photodynamic effects of new lipophilic porphyrin derivatives: efficacy, localisation and cell death pathways.
Photodynamic therapy (PDT) and photodynamic diagnostics (PDD) of cancer are based on the use of non-toxic dyes (photosensitisers) in combination with harmless visible light. This paper reports physicochemical properties, cell uptake, localisation as well as photodynamic efficiency of two novel lipophilic porphyrin derivatives, suitable for use as PDT sensitisers. Both compounds are characterised by high quantum yield of singlet oxygen generation which was measured by time-resolved phosphorescence. Photodynamic in vitro studies were conducted on three cancer cell lines. Results of cell survival tests showed negligible dark cytotoxicity but high phototoxicity. The results also indicate that cell death is dependent on energy dose and time following light exposure. Using confocal laser scanning microscopy both compounds were found to localise in the cytoplasm around the nucleus of the tumour cells. The mode of cell death was evaluated based on the morphological changes after differential staining. In summary, good photostability, high quantum yield of singlet oxygen and biological effectiveness indicate that the examined lipophilic porphyrin derivatives offer quite interesting prospects of photodynamic therapy application.
A.Chelkowski Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice, Poland. kramer_gabriela@yahoo.uk
Gabriela
G
Kramer-Marek
Carlos
C
Serpa
Agnieszka
A
Szurko
Maria
M
Widel
Aleksander
A
Sochanik
Miroslaw
M
Snietura
Piotr
P
Kus
Rui M D
RM
Nunes
Luis G
LG
Arnaut
Alicja
A
Ratuszna
D016923:Cell Death / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes; D015394:Molecular Structure; D010777:Photochemistry; D010778:Photochemotherapy; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D013057:Spectrum Analysis
C513886:5-(4-hexadecyloxyphenyl)-10,15,20-tripyridylporphyrin; C513885:5-(4-hydroxyphenyl)-10,15,20-tritotylporphyrin; D008081:Liposomes; D011166:Porphyrins