Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)2 centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥104 at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC50 values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm-2, 7.8 mW cm-2) and 625-nm red (100 J cm-2, 42 mW cm-2) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm-2, 28 mW cm-2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC50=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC50 values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized 3ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.

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Photoproducts of the Photodynamic Therapy Agent Verteporfin Identified via Laser Interfaced Mass Spectrometry

Molecules ◽

10.3390/molecules25225280 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5280

Author(s):

Chris Furlan ◽

Jacob A. Berenbeim ◽

Caroline E. H. Dessent

Keyword(s):

Mass Spectrometry ◽

Photodynamic Therapy ◽

Macular Degeneration ◽

Gas Phase ◽

Mass Spectrometer ◽

Red Light ◽

Solution Phase ◽

Collision Induced Dissociation ◽

Free Base ◽

New Information

Verteporfin, a free base benzoporphyrin derivative monoacid ring A, is a photosensitizing drug for photodynamic therapy (PDT) used in the treatment of the wet form of macular degeneration and activated by red light of 689 nm. Here, we present the first direct study of its photofragmentation channels in the gas phase, conducted using a laser interfaced mass spectrometer across a broad photoexcitation range from 250 to 790 nm. The photofragmentation channels are compared with the collision-induced dissociation (CID) products revealing similar dissociation pathways characterized by the loss of the carboxyl and ester groups. Complementary solution-phase photolysis experiments indicate that photobleaching occurs in verteporfin in acetonitrile; a notable conclusion, as photoinduced activity in Verteporfin was not thought to occur in homogenous solvent conditions. These results provide unique new information on the thermal break-down products and photoproducts of this light-triggered drug.

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Topical Administration of Tetrasodium-Mesotetraphenyl-Porphinesulfonate (TPPS): Correlation between Drug Penetration and Depth of Necrosis in Skin of Nude Mice following Red Light Irradiation

Tumori Journal ◽

10.1177/030089168707300102 ◽

1987 ◽

Vol 73 (1) ◽

pp. 11-17 ◽

Cited By ~ 2

Author(s):

Renato Marchesini ◽

Elsa Melloni ◽

Giovanni Bottiroli ◽

Salvatore Andreola ◽

Giannino Fava ◽

...

Keyword(s):

Photodynamic Therapy ◽

Nude Mice ◽

Red Light ◽

Local Treatment ◽

Topical Administration ◽

Skin Lesions ◽

Drug Penetration ◽

Suitable Treatment ◽

Epithelial Layers ◽

Photosensitizing Agent

The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2 % solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 am, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.

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TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro

Pharmaceuticals ◽

10.3390/ph13070137 ◽

2020 ◽

Vol 13 (7) ◽

pp. 137 ◽

Cited By ~ 1

Author(s):

Sarah Chamberlain ◽

Houston D. Cole ◽

John Roque ◽

David Bellnier ◽

Sherri A. McFarland ◽

...

Keyword(s):

Lung Cancer ◽

Photodynamic Therapy ◽

Cell Viability ◽

Light Propagation ◽

Residual Disease ◽

Red Light ◽

Optical Surface ◽

Light Fluence ◽

532 Nm

Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber. This TLD1433-mediated PDT induced an EC50 of 1.98 μM (J/cm2) and 4807 μM (J/cm2) for green and red light, respectively. Cells were then treated with 10 µM TLD1433 in a 96-well plate with the OSA using two 2-cm radial diffusers, each transmitted 532 nm light at 50 mW/cm for 278 s. Monte Carlo simulations of the surface light propagation from the OSA computed light fluence (J/cm2) and irradiance (mW/cm2) distribution. In regions where 100% loss in cell viability was measured, the simulations suggest that >20 J/cm2 of 532 nm was delivered. Our studies indicate that TLD1433-mediated PDT with the OSA and light simulations have the potential to become a platform for treatment planning for IO-PDT.

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Photodynamic Therapy for 101 Early Cancers of the Upper Aerodigestive Tract, the Esophagus, and the Bronchi: A Single-Institution Experience

Diagnostic and Therapeutic Endoscopy ◽

10.1155/dte.5.145 ◽

1999 ◽

Vol 5 (3) ◽

pp. 145-154 ◽

Cited By ~ 21

Author(s):

A. Radu ◽

P. Grosjean ◽

Ch. Fontolliet ◽

G. Wagnieres ◽

A. Woodtli ◽

...

Keyword(s):

Photodynamic Therapy ◽

Early Stage ◽

Red Light ◽

Green Light ◽

Tracheobronchial Tree ◽

Aerodigestive Tract ◽

Upper Aerodigestive Tract ◽

Photofrin Ii ◽

Significant Difference ◽

Radical Therapy

Cancer, when detected at an early stage, has a very good probability of being eradicated by surgery or radiotherapy. However, less aggressive treatments also tend to provide high rates of cure without the side effects of radical therapy. We report on the results of our clinical experience with photodynamic therapy (PDT) for the treatment of early carcinomas in the upper aerodigestive tract, the esophagus, and the tracheobronchial tree. Sixty-four patients with 101 squamous cell carcinomas were treated with three different photosensitizers: hematoporphyrin derivative (HPD), Photofrin II, and tetra (m-hydroxyphenyl)chlorin (mTHPC). Seventy-seven (76%) tumors showed a complete rsponse with no recurrence after a mean follow-up period of 27 months. There was no significant difference in terms of cure rates among the three dyes. However, mTHPC has a stronger phototoxicity and induces a shorter skin photosensitization than either of the other photosensitizers. There were eight major complications: three esophagotracheal fistulae after illumination with red light in the esophagus, two esophageal stenoses following 360° circumferential irradiation, and three bronchial stenoses. Illumination with the less penetrating green light and the use of a 180° or 240° windowed cylindrical light distributor render the risk of complications in the esophagus essentially impossible, without reducing the efficacy of the treatment. Therefore, PDT may be considered as a safe and effective treatment for early carcinomas of the upper aerodigestive tract, the esophagus, and the tracheobronchial tree.

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