Investigation of conditions involved in the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment

Smijs, Threes G. M.; Bouwstra, Joke A.; Talebi, Mojgan; Pavel, S.

doi:10.1093/jac/dkm304

Cited by 42 publications

(50 citation statements)

References 35 publications

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“…Pc 4-PDT also demonstrated an excellent safety profile in a phase 1 trial on cutaneous neoplasms (25). Although the susceptibility of T. rubrum to PDT using other photosensitizers has been extensively investigated in vitro, the mechanism of phototoxicity has not been clearly defined (2,9,(26)(27)(28). In this study, we showed that a common dose of Pc 4-PDT can induce cell death in microconidia (terbinafine-sensitive and -resistant strains of T. rubrum).…”

mentioning

confidence: 77%

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Lam

Dimaano

Oyetakin-White

et al. 2014

Antimicrob Agents Chemother

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dTrichophyton 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 agerelated 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(CH 3 ) 2 (CH 2 ) 3 N(CH 3 ) 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 M 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. Utilizing mainly keratin for their source of energy, dermatophytes can cause dermatophytosis or tinea of the skin, hair, and nails that impact the quality of life of infected patients, especially in immunocompromised individuals. Trichophyton rubrum is the main culprit of superficial mycosis of the nail (onychomycosis), which is often long lasting and has a high incidence of recurrence. Onychomycosis affects 10% of the general population, 20% of the population older than 60 years, 50% of people older than 70 years, and 30% of diabetic patients, and it can often result in pain, disability, and psychosocial stress, therefore significantly reducing quality of life (1-3). The conventional treatments involve excruciating surgical nail avulsion and toxic systemic antifungal drugs. Topical therapy is a less invasive and hence more attractive treatment for the eradication of fungal infection. However, dismal patient compliance often contributes to the high rate of unsuccessful treatment (4). It is for these reasons that alternative therapeutic agents need to be developed that can effectively target T. rubrum without significantly harming the host.In vitro studies have dem...

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mentioning

confidence: 77%

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Lam

Dimaano

Oyetakin-White

et al. 2014

Antimicrob Agents Chemother

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“…Photosensitizers, such as methylene blue and toluidine blue, have been shown to be a vital adjunct when using visible light to treat bacterial and fungal infections [19][20][21][22]. They are chosen on the basis of their charge, ability to be non-toxic without illumination (dark toxicity) and the ability to become genotoxic or mutagenic following irradiation [23].…”

Section: Biophotonicsmentioning

confidence: 99%

An in vitro study of the photodynamic effect of rose bengal on trichophyton rubrum

Cronin

Moffitt

Mawad

et al. 2012

Journal of Biophotonics

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Onychomycosis, a fungal infection of the finger or toenails, is predominantly caused by Trichophyton rubrum. Treatment is difficult due to high recurrence rates and problems with treatment compliance. For these reasons, alternative therapies are needed. Here we describe the photoactivation of Rose Bengal (RB) using a green laser (λ = 532 nm) at fluences of 68, 133 and 228 J/cm(2) , and assess its fungicidal activity on T. rubrum spore suspensions. A 140 µM RB solution was able to induce a fungicidal effect on T. rubrum when photosensitized with the fluence of 228 J/cm(2) . RB photosensitization using a green laser provides a potential novel treatment for T. rubrum infections.

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“…141,142 Other nonhematoporphyrin-derived photosensitizers (Sylsens B being the most effective) have also been shown to be efficacious in the treatment of onychomycosis. 143,144 Major concerns regarding effective drug penetration through thick, hyperkeratotic ungual barriers have led to introduction of new delivery methods involving iontophoretic and ultrasound devices, which enable increased nail bed permeability. 145,146 Most recently, one patient with treatment-resistant onychomycosis was successfully pretreated with a micro motor pneumatic diamond drill device and subsequent ALA-PDT with red light.…”

Section: Pdt In Microbial Diseases Virusesmentioning

confidence: 99%

Current Evidence and Applications of Photodynamic Therapy in Dermatology

2015

Journal of the Dermatology Nurses' Association

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Abstract:In photodynamic therapy (PDT) a photosensitizer -a molecule that is activated by light -is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT.

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Investigation of conditions involved in the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment

Cited by 42 publications

References 35 publications

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

An in vitro study of the photodynamic effect of rose bengal on trichophyton rubrum

Current Evidence and Applications of Photodynamic Therapy in Dermatology

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