Non-aggregated Ga(III)-phthalocyanines in the photodynamic inactivatio planktonic and biofilm cultures of pathogenic microorganisms

Abstract

Visible light-absorbing cationic water-soluble gallium(III) phthalocyanines (GaPcs) peripherally substituted with four and eight methylpyridyloxy groups were synthesized and investigated as antimicrobial photodynamic sensitizers. The inserted large gallium ion in the phthalocyanine ligand is axially substituted by one hydroxyl group which prevents aggregation of the complexes in aqueous solution. The cellular uptake and the photodynamic activity for the representative strains of the Gram positive bacteria methicillin-resistant Staphylococcus aureus(MRSA) and Enterococcus faecalis, of the Gram negative bacterium Pseudomonas aeruginosa and of the fungus Candida albicans in planktonic phase were studied. The tetra-methylpyridyloxy substituted GaPc1 showed lower cellular uptake compared to the octa-methylpyridyloxy substituted GaPc2. The photodynamic activity of the GaPcs was studied in comparison to methylene blue (MB) and a photodynamically active Zn(II)-phthalocyanine with the same substitution (ZnPcMe). Photodynamic treatment with 3.0 μM GaPc1 at mild light conditions (50 J cm(-2), 60 mW cm(-2)) resulted in a high photoinactivation of the microorganisms in the planktonic phase nevertheless the dark toxicity of GaPc1 towards MRSA and E. faecalis. GaPcs against fungal biofilm grown on polymethylmethacrylate (PMMC) resin showed a complete inactivation at a higher concentration of GaPc2 (6.0 μM) and of the referent sensitizer ZnPcMe. However, the bacterial biofilms were not susceptible to treatment of GaPcs with only 1-2 log reduction of the biofilm. The bacterial biofilm E. faecalis was effectively inactivated only with MB. The water-soluble octa-methylpyridyloxy substituted GaPc2 has a potential value for photodynamic treatment of C. albicans biofilms formed on denture acrylic resin.

Susceptibility of clinical isolates of Candida to photodynamic effects of curcumin

“…For this reason, there has been an increased interest in developing PDT for local infections treatment. Different types of PS have been proposed in laboratory investigations, including porphyrins [14,15], phenothiazine dyes [16,17], chlorins [18,19], and phthalocyanines [20]. However, complete killing of the microorganisms is not frequently achieved and some of the available PS showed limited effectiveness against Candida biofilms and animal models of candidiasis [15,21].…”

Photodynamic inactivation of biofilms formed by Candida spp., Trichosporon mucoides, and Kodamaea ohmeri by cationic nanoemulsion of zinc 2,9,16,23-tetrakis(phenylthio)-29H, 31H-phthalocyanine (ZnPc)

“…The analysis of the efficiency of cationic and anionic ZnPc irradiated by argon-pumped dye laser system (60 J cm -2 ) on C. albicans planktonic culture was carried out by Mantareva et al [28]. The cationic ZnPc was more efficient than anionic ZnPc, with total reduction of 10 6 -10 8 cells/ml of C. albicans compared to a 1-2 log reduction of cells, respectively, which is due to the fact that cationic phthalocyanines exhibit better adhesion to the cellular membrane [29].…”

“…Mantareva et al [29] evaluated the photodynamic effect of two phthalocyanines, hydroxygallium(III) 2,9,16,23-tetrakis-[3-(N-methyl)pyridyloxy]-phthalocyanine tetraiodide (GaPc1) and hydroxygallium(III) 2,3,9,10,16,17,23,24-octakis-(3-pyridyloxy)-phthalocyanine (GaPc2), with LED (50 J cm -2 ) in comparison to methylene blue and a water-soluble tetramethylpyridyloxy-substituted Zn(II)-phthalocyanine (ZnPcMe) on C. albicans biofilms grown on polymethylmethacrylate resin. Complete photodynamic inactivation of biofilms with GaPc2 and ZnPcMe was found.…”

“…They are characterized by far-red wavelength absorption (> 670 nm), long triplet lifetime (∼1 ms), high quantum yields of singlet oxygens (> 0.2), and low dark toxicity [28][29][30]. The main advantage in the use of phthalocyanine as photosensitizer is the fact that this family of dyes could act by the two classical PDI mechanisms of radical production (type I) or singlet oxygen (type II) [31].…”

“…The charge of the photosensitizer is an important factor in determining its effective photodynamic action and whether cells uptake it. Gram-negative bacteria and fungi are resistant to anionic and neutral phthalocyanines [28,29]. In this study, the photodynamic action of a nanostructured formulation cationic zinc 2,9,16,23-tetrakis (phenylthio)-29H,31H-phthalocyanine (ZnPc) was used for inactivating biofilms of different Candida species, T. mucoides, and K. ohmeri.…”