Photodynamic Inactivation of Candida albicans Sensitized by tri- and tetra-cationic Porphyrin Derivatives

M. PAULA CORMICK, M. GABRIELA ÁLVAREZ, MARISA ROVERA AND EDGARDO N. DURANTINI

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

Elsevier

Año: 2009 vol. 44 p. 1592 - 1599

0223-5234

The photodynamic action of 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyriniodide (TFAP3þ) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP4þ) has been studied in vitro on Candida albicans. The results of these cationic porphyrins were compared with those of 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS4), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of w1.4 nmol/106 cells, when the cellular suspensions were incubated with 5 mM sensitizer for 30 min. In contrast, TPPS4 is poorly uptaken by yeast cells. The fluorescence spectra of these sensitizers into the cells confirm this behaviour. The amount of porphyrin binds to cells is dependent on both sensitizer concentrations (1–5 mM) and cells densities (106–108 cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a w5 log decrease of cell survival, when the cultures are treated with 5 mM of cationic porphyrin and irradiated for 30 min. However, the photocytotoxicity decreases with an increase in the cell density, according to its low binding to cells. Under these conditions, the photodynamic activity of TFAP3þ is quite similar to that produced by TMAP4þ, whereas no important inactivation effect was found for TPPS4. The high photodynamic activity of cationic porphyrins was confirmed by growth delay experiments. Thus, C.albicans cell growth was not detected in the presence of 5 mM TFAP3þ. Photodynamic inactivationcapacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agarsurfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was notobserved after 3 h irradiation, indicating a complete inactivation of yeast cells. Therefore, these resultsindicate that these cationic porphyrins are interesting sensitizers for photodynamic inactivation of yeasts in liquid suspensions or in localized foci of infection.3þ) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP4þ) has been studied in vitro on Candida albicans. The results of these cationic porphyrins were compared with those of 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS4), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of w1.4 nmol/106 cells, when the cellular suspensions were incubated with 5 mM sensitizer for 30 min. In contrast, TPPS4 is poorly uptaken by yeast cells. The fluorescence spectra of these sensitizers into the cells confirm this behaviour. The amount of porphyrin binds to cells is dependent on both sensitizer concentrations (1–5 mM) and cells densities (106–108 cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a w5 log decrease of cell survival, when the cultures are treated with 5 mM of cationic porphyrin and irradiated for 30 min. However, the photocytotoxicity decreases with an increase in the cell density, according to its low binding to cells. Under these conditions, the photodynamic activity of TFAP3þ is quite similar to that produced by TMAP4þ, whereas no important inactivation effect was found for TPPS4. The high photodynamic activity of cationic porphyrins was confirmed by growth delay experiments. Thus, C.albicans cell growth was not detected in the presence of 5 mM TFAP3þ. Photodynamic inactivationcapacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agarsurfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was notobserved after 3 h irradiation, indicating a complete inactivation of yeast cells. Therefore, these resultsindicate that these cationic porphyrins are interesting sensitizers for photodynamic inactivation of yeasts in liquid suspensions or in localized foci of infection.