Photodynamic therapy in dermatology: a review

Choudhary, Sonal; Nouri, Keyvan; Elsaie, Mohamed L.

doi:10.1007/s10103-009-0716-x

Cited by 137 publications

(92 citation statements)

References 60 publications

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“…Photodynamic therapy (PDT) is now a well-established treatment modality for cutaneous carcinomas camptothecin (1,5), but melanotic melanomas generally have a poor response to PDT owing to several characteristics that confer chemoresistance such as high antioxidant activity (2). The presence of melanin permits the absorption of UV and spectral light by pigmented melanoma, reducing photosensitizer excitation.…”

Section: Discussionmentioning

confidence: 99%

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Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Sparsa¹,

Bellaton²,

Naves³

et al. 2012

Oncology Reports

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Abstract. Photodynamic therapy (PDT) is now a well-established treatment modality for cutaneous carcinomas and is based on the administration of a light-activated drug followed by illumination of the pathological area. The treatment of metastatic melanoma remains a therapeutic challenge. To define the possible role of melanin in relative phototoxicity of 5-aminolevulinic acid (5-ALA), a photosensitizer used in PDT in vivo, we studied cell death in two variants (with or without melanin, B16F10 and B16G4F cells, respectively) of a melanoma cell line. Concentrations of 5-Ala up to 10 mM induced similar cytostatic effects in the B16G4F and B16F10 cells. PDT and high 5-ALA concentrations induced photocytotoxicity in both melanoma cell lines (at 10 mM for B16F10 cells and at 5 mM for B16G4F cells). Cell death corresponded to p53-dependent apoptotic signaling in pigmented B16F10 cells, whereas an autophagic response leading to a caspase-independent death was detected in nonpigmented B16G4F cells. Therefore, the PDT-induced cell death pathway appeared to correlate with melanin synthesis capacity in melanoma cells. To reduce the cytotoxicity of 5-ALA without irradiation, a low drug concentration could be used. Consequently, in combination with current therapeutics, a moderate concentration of 5-ALA and PDT may constitute a supplementary promising approach to eliminate metastatic melanoma. IntroductionPhotodynamic therapy (PDT) has been used in clinical application for many years, either systemically, or locally or topically applied to a patient bearing a lesion (cancerous or not). PDT with systemic photosensitizers has been used to treat a range of internal malignancies (lung and brain cancers) and for skin cancers (1). This cancer treatment is approved by many countries for the treatment of non-melanotic skin cancers such as basal cell carcinomas and Bowen's disease. PDT does not seem to be an appropriate treatment of melanotic melanoma in vivo, and several reasons can justify this low use. Almost all melanomas overexpress the classical ATP-binding cassette transporters (ABC protein family), leading to drug release into the extracellular medium and to the resistance by tumor cells. The antioxidant activity of melanoma is much higher than observed in other skin cancers (basal and squamous carcinomas) reducing the cytotoxic effect of ROS generated by PDT (2). Nearly all photosensitizers (PS) show a significant absorbance in ultraviolet (UV) wavelengths, while melanin absorbs a large portion of the light intended to activate PS. The light absorption by pigment strongly reduces its penetration into the tumor. Studies have been carried out with pigmented or amelanotic melanoma cells suggesting that amelanotic cells may be more susceptible to PDT (2). Among the molecules used in PDT, 5-aminolevulinic acid (5-ALA) is not itself a photosensitizer and instead it is used as a prodrug leading to the accumulation of protoporphyrin IX in the mitochondria inducing damage and subsequently cell death after light irradiation (3).It is w...

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Section: Discussionmentioning

confidence: 99%

“…PDT with systemic photosensitizers has been used to treat a range of internal malignancies (lung and brain cancers) and for skin cancers (1). This cancer treatment is approved by many countries for the treatment of non-melanotic skin cancers such as basal cell carcinomas and Bowen's disease.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Sparsa¹,

Bellaton²,

Naves³

et al. 2012

Oncology Reports

View full text Add to dashboard Cite

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“…19 Photodynamic (PD) stress has been the subject of intense research in recent decades due to its therapeutic applications in PDT of cancer, age-related macular degeneration, microbial infections or dermatological diseases, such as actinic keratosis or acne vulgaris. [20][21][22][23][24][25] Several of the cellular events that occur in the phase comprised between the primary photo-oxidative damage and the final therapeutic effect, which is cell death and eradication of diseased tissue, are modulated by secondary ROS. Secondary ROS can extend the initial photodamage intracellularly, as seen by Ouedrago et al 26 where lipid hydroperoxides produced in the cell membrane after photooxidation using deuteroporphyrin can spread the oxidative damage within the cells and produce nuclear DNA damage.…”

Section: Hyp-pd Mediated Er Photodamage Propagates Ros and Autophagy mentioning

confidence: 99%

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

et al. 2012

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Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis

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“…Topical photodynamic therapy (PDT) has been applied to almost every type of superficial nonmelanoma skin cancer and numerous benign skin disorders [1][2]. PDT is based on the administration of a photosensitizing drug and its selective retention in malignant tissue and its subsequent activation by light at specific wavelengths, causing cell death by the production of free radicals and/or reactive oxygen species [3,4].…”

Section: Introductionmentioning

confidence: 99%

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

Praça¹,

Medina²,

Petrilli³

et al. 2012

CNANO

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Topical photodynamic therapy (PDT) has been applied to almost all types of nonmelanoma skin cancer and numerous superficial benign skin disorders. Strategies to improve the accumulation of photosensitizer in the skin have been studied in recent years. Although the hydrophilic phthalocyanine zinc compound, zinc phthalocyanine tetrasulfonate (ZnPcSO4) has shown high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain tumors and eye conditions, its use in topical skin treatment is currently limited by its poor skin penetration. In this study, nanodispersions of monoolein (MO)-based liquid crystalline phases were studied for their ability to increase ZnPcSO4 uptake by the skin. Lamellar, hexagonal and cubic crystalline phases were prepared and identified by polarizing light microscopy, and the nanodispersions were analyzed by dynamic light scattering. In vitro skin penetration studies were performed using a Franz's cell apparatus, and the skin uptake was evaluated in vivo in hairless mice. Aqueous dispersions of cubic and hexagonal phases showed particles of nanometer size, approximately 224 ±10 nm and 188 ± 10 nm, respectively. In vitro skin retention experiments revealed higher fluorescence from the ZnPcSO4 in deeper skin layers when this photosensitizer was loaded in the hexagonal nanodispersion system when compared to both the cubic phase nanoparticles and the bulk crystalline phases (lamellar, cubic and hexagonal). The hexagonal nanodispersion showed a similar penetration behavior in animal tests. These results are important findings, suggesting the development of MO liquid crystal nanodispersions as potential delivery systems to enhance the efficacy of topical PDT.Keywords: Liquid crystalline phases, nanodispersion, skin cancer, skin penetration, photodynamic therapy, zinc phthalocyanine. INTRODUCTIONTopical photodynamic therapy (PDT) has been applied to almost every type of superficial nonmelanoma skin cancer and numerous benign skin disorders [1][2]. PDT is based on the administration of a photosensitizing drug and its selective retention in malignant tissue and its subsequent activation by light at specific wavelengths, causing cell death by the production of free radicals and/or reactive oxygen species [3,4]. Numerous strategies have been studied in recent years in attempts to improve the accumulation of photosensitizers and their precursors in the skin, including the use of microemulsions [5] [13][14][15]. Lipophilic phthalocyanines (e.g., zinc and chloroaluminum compounds) have been widely used as photosensitizers in preclinical studies of PDT for the treatment of skin cancer [16,17]. In contrast, the water-soluble zinc phthalocyanine tetrasulfonate (ZnPcSO 4 ) has displayed high photodynamic efficiency and reduced phototoxic side effects in the treatment of brain and ocular tumors [18]. However, with exception of a few studies [19][20][21], there is a lack of data on the application of ZnPcSO 4 in PDT for skin cancer.Their ability to control the release of dru...

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Photodynamic therapy in dermatology: a review

Cited by 137 publications

References 60 publications

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Photodynamic treatment induces cell death by apoptosis or autophagy depending on the melanin content in two B16 melanoma cell lines

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration

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