Photodynamic inactivation of Candida albicans sensitized by tri- and tetra-cationic porphyrin derivatives

Eur J Med Chem. 2009 Apr;44(4):1592-9. doi: 10.1016/j.ejmech.2008.07.026. Epub 2008 Jul 26.

Abstract

The photodynamic action of 5-(4-trifluorophenyl)-10,15,20-tris(4-trimethylammoniumphenyl)porphyrin iodide (TFAP(3+)) and 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin p-tosylate (TMAP(4+)) 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 (TPPS(4-)), which characterizes an anionic sensitizer. In vitro investigations show that these cationic porphyrins are rapidly bound to C. albicans cells, reaching a value of approximately 1.4 nmol/10(6) cells, when the cellular suspensions were incubated with 5 microM sensitizer for 30 min. In contrast, TPPS(4-) 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 microM) and cells densities (10(6)-10(8) cells/mL). Photosensitized inactivation of C. albicans cellular suspensions increases with sensitizer concentration, causing a approximately 5 log decrease of cell survival, when the cultures are treated with 5 microM 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 TFAP(3+) is quite similar to that produced by TMAP(4+), whereas no important inactivation effect was found for TPPS(4)(-). 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 microM TFAP(3+). Photodynamic inactivation capacities of these sensitizers were also evaluated on C. albicans cells growing in colonies on agar surfaces. Cationic porphyrins produce a growth delay of C. albicans colonies and viability of cells was not observed after 3 h irradiation, indicating a complete inactivation of yeast cells. Therefore, these results indicate that these cationic porphyrins are interesting sensitizers for photodynamic inactivation of yeasts in liquid suspensions or in localized foci of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Buffers
  • Candida albicans / cytology
  • Candida albicans / drug effects*
  • Candida albicans / metabolism
  • Candida albicans / radiation effects
  • Candidiasis / drug therapy
  • Cell Proliferation / drug effects
  • Cells, Immobilized / cytology
  • Cells, Immobilized / drug effects
  • Culture Media
  • Light
  • Photochemical Processes
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / metabolism
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / therapeutic use
  • Porphyrins / chemistry*
  • Porphyrins / metabolism
  • Porphyrins / pharmacology*
  • Porphyrins / therapeutic use
  • Spectrometry, Fluorescence

Substances

  • Buffers
  • Culture Media
  • Photosensitizing Agents
  • Porphyrins