Molecular characteristics of the photosensitizer TONS504: Comparison of its singlet oxygen quantum yields and photodynamic antimicrobial effect with those of methylene blue

Synergistic effect of TONS504-mediated photodynamic antimicrobial chemotherapy and additives widely contained in ophthalmic solutions: benzalkonium chloride and ethylenediaminetetraacetic acid

“…Considering that PAE depends on 1 O 2 generation, we hypothesized that adding surfactant agents to prevent TONS504 self-aggregation might increase its PAE. In addition, we found that Pseudomonas aeruginosa-a Gram-negative bacteria-displayed greater resistance to TONS504-PACT than Staphylococcus aureus-a Gram-positive bacteria [13]. Given that the outer membrane of Gram-negative bacteria contributes to their resistance to PACT [14], disrupting the outer membrane would enhance the PAE of TONS504 on Gram-negative bacteria.…”

“…A semiconductor laser system (PCTH195) that delivers light centered on a wavelength of 665 nm was obtained from Unitac Co., Ltd. (Hiroshima, Japan). The irradiance and irradiation time followed those of our previous study (irradiance: 0.055 W/cm 2 , irradiation time: 9 min continuously, and total light energy: 30 J/cm 2 ) [13].…”

“…The culture condition followed that of a previous study with some modifications [13]. Briefly, S. aureus (NITTE Biological Resource Center 14462, corresponding to American Type Culture Collection 25923) and P. aeruginosa (American Type Culture Collection 27853), were separately grown in a liquid medium containing hipolypepton (Nihon Pharmaceutical, Tokyo, Japan), magnesium sulfate heptahydrate, and dried yeast extract (Nacalai Tesque, Kyoto, Japan) at 37 °C overnight in a shaking incubator.…”

“…A newly developed photosensitizer, named TONS504 [13,17-bis(1-carboxyethyl)-carbamoyl-(3-methylpyridine)-3-(1,3-dioxane-2-yl) methylidene-8-ethenyl-2-hydroxy-2,7,12,18-tetramethyl chlorine, di-N-methyl iodide (C 51 H 58 N 8 O 5 I 2 )], is a hydrophilic and cationic chlorine derivative. The photodynamic antimicrobial effect (PAE) of TONS504 has been proved for various keratitis-causative pathogens in vitro and in vivo [7][8][9][10][11][12][13]. We recently found that TONS504 effectively generates 1 O 2 , but simultaneously it has a high tendency to self-aggregate and likely decreases 1 O 2 production by the photosensitizer [13].…”

“…The photodynamic antimicrobial effect (PAE) of TONS504 has been proved for various keratitis-causative pathogens in vitro and in vivo [7][8][9][10][11][12][13]. We recently found that TONS504 effectively generates 1 O 2 , but simultaneously it has a high tendency to self-aggregate and likely decreases 1 O 2 production by the photosensitizer [13]. Considering that PAE depends on 1 O 2 generation, we hypothesized that adding surfactant agents to prevent TONS504 self-aggregation might increase its PAE.…”