title: Silicon phthalocyanine 4 phototoxicity in Trichophyton rubrum.
abstract: Trichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] in T. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 μM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm(2) reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.
authors.affiliation: Department of Dermatology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA Case Skin Diseases Research Center, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Minh
authors.initials: M
authors.lastname: Lam
authors.affiliation: Department of Dermatology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Dimaano
authors.affiliation: Department of Dermatology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Oyetakin-White
authors.affiliation: Center for Medical Mycology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Retuerto
authors.affiliation: Center for Medical Mycology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Chandra
authors.affiliation: Center for Medical Mycology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: Center for Medical Mycology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.affiliation: Department of Dermatology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA Case Skin Diseases Research Center, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA Louis-Stokes VA Medical Center, Cleveland, Ohio, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cooper
authors.affiliation: Department of Dermatology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA Case Skin Diseases Research Center, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, USA Louis-Stokes VA Medical Center, Cleveland, Ohio, USA elma.baron@case.edu.
authors.forename: Elma D
authors.initials: ED
authors.lastname: Baron
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D009281:Naphthalenes / Q000494:pharmacology; D017646:Organosilicon Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000382:microbiology; D000077291:Terbinafine; D013778:Tetrazolium Salts; D014005:Tinea / Q000188:drug therapy*; D014249:Trichophyton / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
chemical_list: D000935:Antifungal Agents; D007211:Indoles; D009281:Naphthalenes; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; C082854:silicon phthalocyanine; D000077291:Terbinafine