Photodynamic Therapy with Pc 4 Induces Apoptosis of <i>Candida albicans</i>

Lam, Minh; Jou, Paul C.; Lattif, Ali Abdul; Lee, Yoojin; Malbasa, Christi L.; Mukherjee, Pranab K.; Oleinick, Nancy L.; Ghannoum, Mahmoud A.; Cooper, Kevin D.; Baron, Elma D.

doi:10.1111/j.1751-1097.2011.00938.x

Cited by 52 publications

(38 citation statements)

References 36 publications

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“…In addition, the Pc 4 fluorescence appears to be site specific, which is consistent with previous studies which showed that Pc 4 preferentially binds to intracellular organelles once the cellular uptake has occurred (31,39). To examine whether the mitochondrion is one of the organelles to which Pc 4 binds, we coloaded the Pc 4-treated microconidia and hyphae with a commercially available mitochondrion-specific probe.…”

Section: Discussionsupporting

confidence: 61%

“…Within 5 h following irradiation of Pc 4-treated microconidia and hyphae, their metabolic activities were assayed using the colorless sodium salt of XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) (Sigma-Aldrich, St. Louis, MO), which is converted by mitochondrial dehydrogenases of viable microconidia/hyphae into a water-soluble orange formazan derivative through the reduction of the tetrazolium ring of XTT. The absorbance of the resulting orange solution was measured using a spectrophotometer (Spectronic Genesys 5; Analytical Instruments, Golden Valley, MN) at a wavelength of 492 nm as previously described (30,31). Note again that some microconidia may have become hyphal during the overnight Pc 4 incubation in complete medium.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Lam

Dimaano

Oyetakin-White

et al. 2014

Antimicrob Agents Chemother

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“…The light therapeutic properties studies with antimicrobial purpose are primarily motivated by resistance cases of conventional antimicrobial 3,6,[11][12][13][14] . The need to overcome these deficiencies led to the exploration of Petri dishes containing Agar Sabouraud Dextrose culture medium.…”

Section: Discussionmentioning

confidence: 99%

“…The most important factor governing the PDT results is how the FS interacts with the cells in the tissue or target lesion, and the key aspect of this interaction is related to the FS intracellular location. The incubation time is required to allow the drug to be absorbed by the microorganism and accumulate in the cell structures 20 , such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membrane 3 . During irradiation, it is necessary that FS is already located inside the cell, because the singlet oxygen, formed after light application, presents minimal diffusion (100nm) and cytotoxic effect only in the place where it is produced 15 .…”

Section: Discussionmentioning

confidence: 99%

Photoinactivation of Candida albicans using methylene blue as photosensitizer

Sousa

Queiroga

Kocerginsky³

et al. 2015

RGO, Rev. Gaúch. Odontol.

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ObjectiveTo evaluate the effect of photodynamic therapy in the inactivation of Candida albicans planktonic cells, using methylene blue, 150 mg/mL, as a photosensitizer. Methods Aliquots of 100 (μg/mL of the fungal suspension in a 10 Results At the concentration of 150 μg/mL, and time of 5 min incubation, the reduction was significant (p˂0.05). In the absence of irradiation, methylene blue produced no reduction in CFU/mL. Conclusion Photodynamic Therapy presented antifungal effect against Candida albicans and can be used as an adjunct to conventional treatment.Indexing terms: Candida albicans. Methylene blue. Photochemotherapy. RESUMO ObjetivoAvaliar o efeito da terapia fotodinâmica na inativação de células planctônicas de Candida albicans, empregando azul de metileno a 150 µg/ mL como fotossensibilizador. MétodosAlíquotas de 100 µg/mL da suspensão do fungo na concentração de 10 6 células/mL foram semeadas em placas de microtitulação com 96 poços, onde foi depositado o mesmo volume de azul de metileno, permanecendo por um período de pré-irradiação de 5 min. Em seguida, aplicou-se luz laser de baixa potência (comprimento de onda: 660 nm, potência: 100 mW e dose: 426 J/cm 2 ) por 128s, utilizando um Laser semicondutor portátil. Experimentos controles foram realizados, sem iluminação e na ausência de azul de metileno, outro na presença de azul de metileno sem iluminação e com iluminação, substituindo o fotossensibilizador por solução salina. De cada condição experimental, diluições em série (10 -1 a 10 -3 ) foram obtidas e alíquotas de 25 μL foram plaqueadas em duplicata em Agar Sabouraud Dextrose. Após este período, o número de unidades formadoras de colônias por mililitro (CFU/mL) foi determinado e os dados foram submetidos à análise de variância e teste de Kruskal Wallis (p <0,05).Resultados Na concentração de 150 μg/mL e tempo de 5 min de incubação, a redução foi significativa (p<0,05). Na ausência de irradiação, o azul de metileno não produziu redução de CFU/mL. ConclusãoA Terapia Fotodinâmica apresentou efeito antifúngico contra Candida albicans, podendo ser utilizada como coadjuvante ao tratamento convencional.Termos de indexação: Candida albicans. Azul de metileno. Fotoquimioterapia. Therefore, this study aims to evaluate, in vitro, the photosensitizing effects in Candida albicans with laser radiation, using methylene blue as a photosensitizer. Photoinactivation of Candida albicans using methylene blue as photosensitizer

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“…Numerous published studies have shown PDT to be highly effective in the in vitro inactivation of fungi (19,20,31). In addition, it is considered that the development of resistance to PDT by microbes is an unlikely event, because PDT is typically a multitarget process, which is a difference between PDT and most other antifungal drugs (22).…”

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confidence: 99%