Improved Simulated-Daylight Photodynamic Therapy and Possible Mechanism of Ag-Modified TiO2 on Melanoma.

Simulated-daylight photodynamic therapy (SD-PDT) may be an efficacious strategy for treating melanoma because it can overcome the severe stinging pain, erythema, and edema experienced during conventional PDT. However, the poor daylight response of existing common photosensitizers leads to unsatisfactory anti-tumor therapeutic effects and limits the development of daylight PDT. Hence, in this study, we utilized Ag nanoparticles to adjust the daylight response of TiO2, acquire efficient photochemical activity, and then enhance the anti-tumor therapeutic effect of SD-PDT on melanoma. The synthesized Ag-doped TiO2 showed an optimal enhanced effect compared to Ag-core TiO2. Doping Ag into TiO2 produced a new shallow acceptor impurity level in the energy band structure, which expanded optical absorption in the range of 400-800 nm, and finally improved the photodamage effect of TiO2 under SD irradiation. Plasmonic near-field distributions were enhanced due to the high refractive index of TiO2 at the Ag-TiO2 interface, and then the amount of light captured by TiO2 was increased to induce the enhanced SD-PDT effect of Ag-core TiO2. Hence, Ag could effectively improve the photochemical activity and SD-PDT effect of TiO2 through the change in the energy band structure. Generally, Ag-doped TiO2 is a promising photosensitizer agent for treating melanoma via SD-PDT.

Measurements of illuminance in simulated daylight photodynamic therapy.

BACKGROUND: Simulated daylight photodynamic therapy (SDL-PDT) is a new treatment alternative for actinic keratosis. The aim of this study was to show how the illuminance that reaches the target skin area during SDL-PDT depends on the spatial positioning of the patient. METHODS: In this technical validation study, illuminance from the SDL-PDT system IndoorLux© was measured at different angles, directions, and distances from the light sources corresponding to potential target skin areas. Using two different photometers, data from 63 measuring points at seven specific distances from the ceiling were collected at 0°, 45°, and 90° angles, respectively. Illuminance levels ≥12,000 lux were regarded as adequate. Hotspots were defined as adequate measurements in all directions at a specific measuring point at distances of 1.3, 1.5, and 1.8 m from the light sources (i.e., the most common patient treatment positions). RESULTS: Adequate illuminance levels were more common with photometer 1 (73%) than photometer 2 (57%). Almost all illuminance levels were adequate at a 0° angle with both photometers. Adequate illuminance levels were observed at 82-93% of the measuring points at a 45° angle and 22-47% at a 90° angle. Hotspots were registered with both photometers at all measuring points at 0°; 59-79% of the measuring points at 45°; and 0-21% at 90°. CONCLUSION: Patient positioning is important during SDL-PDT. Adequate illuminance is achieved if target skin areas are positioned at 0°-45° angles relative to the light sources, but not at 90° angles.

[Successful treatment of cutaneous leishmaniasis with simulated daylight photodynamic therapy]. / Erfolgreiche Therapie der kutanen Leishmaniose mit simulierter Tageslicht-photodynamischer Therapie.

A 5-year-old Syrian boy , presented with a complex cutaneous leishmaniasis (CL) of the right ankle caused by Leishmania (L.) tropica. The patient received photodynamic therapy (PDT; 6 cycles with application of 5­aminolevulinic acid and foil occlusion for 3 h). Due to pain during exposure to red light, exposure was continued with simulated daylight (sDL-PDT). The lesion healed with an atrophic scar. Due to fewer side effects and less pain, sDL-PDT seems to be a good therapeutic strategy for CL caused by L. tropica.

A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis.

BF-200 ALA is a combination of a nanoscale-lipid vesicle formulation and the prodrug 5-aminolevulinic acid (5-ALA). The nanoemulsion stabilizes the prodrug and enhances its penetration through the stratum corneum. It has shown excellent therapeutic results in both lesion and field-directed photodynamic therapy of actinic keratosis (AK). AK is an early form of epidermal neoplasia and a precursor of invasive cutaneous squamous cell carcinoma. It is characterized by the combination of visible neoplastic lesions and surrounding tissue also harboring tumorigenic UV-induced mutations: a concept called field cancerization. A selective, field-directed treatment is ideal to meet the requirements of field change. Here, we review the clinical data on BF-200 ALA for AK along with a summary of molecular mechanisms and future perspectives.

Is a 4 J/cm2 PpIX-Weighted Simulated Daylight (SDL-PDT) Dose Still Efficient for Photodynamic Therapy of Actinic Keratosis?

Background: Several solutions are now proposed to provide indoor illumination with so-called artificial white light or simulated daylight (SDL-PDT), resulting in an effective treatment for actinic keratosis (AK). However, the optimal PpIX-weighted light dose is still debated. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose and is a key parameter for the efficacy of the treatment. Objectives: The paper aims to report the clinical outcomes of SDL-PDT when using the PpIX-weighted light dose of 4 J/cm2, in patients treated for AK lesions of the scalp or the face at our medical dermatology center (ClinicalTrials.gov NCT052036). Methods: A total of 30 patients (16 males, 14 females), with a mean age of 71.0 ± 10.2, with phototype 1 (16 patients) and phototype 2 (14 patients) with grade I-II AK were treated with a drug light interval (DLI) of 10 min and a light exposure of 35 min (Dermaris, Surgiris, Croix, France), corresponding to a PpIX-weighted light dose of 4 J/cm2. The primary endpoint was the cure rate of patients at six months post-treatment. Secondary endpoints included scores of pain, erythema, crusts, and discomfort during or/and post the treatment. Results: In total, 762 AK were treated. Six months following treatment, the cure rate of the patients was 77%. The median pain score was less than 1 out of 10 for most of the patients. Erythema was observed in all patients and lasted 3 days (±1.5 day). Crusts were seen in 28 patients. Discomfort was reported as mild or less in more than 97% of patients. Conclusions: The shortening of the PpIX-weighted light dose to 4 J/cm2, corresponding to an illumination duration of 35 min with the Dermaris, does not modify the efficacy of the SDL-PDT. This observation is in agreement with recent published data demonstrating that the light dose can be reduced. Furthermore, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.

No room for pain: A prospective study showing effective and nearly pain-free treatment of actinic keratosis with simulated daylight photodynamic therapy (SDL-PDT) using the IndoorLux® System in combination with BF-200 ALA (Ameluz®).

BACKGROUND: Photodynamic therapy (PDT) with natural daylight is effective and less painful than conventional PDT when treating actinic keratosis (AK), however its weather dependency is restrictive. This prospective open-label observational single-arm study examined efficacy and safety of simulated daylight (SDL)-PDT using the IndoorLux® system in combination with 5-aminolevulinic acid gel (BF-200 ALA). METHODS: 12 patients with mild/moderate AK on the face or scalp received two SDL-PDTs. BF-200 ALA was applied prior to a 2 h illumination with the IndoorLux® System. Patients evaluated pain during and after SDL-PDT on visual analogue scales (VAS). Primary endpoint was lesion count reduction three months after the second SDL-PDT. Secondary endpoint was pain during and after illumination. RESULTS: Median individual clearance rate was 83.75% (66.7-100.0%); 33.3% of the patients and 84.9% of the lesions were completely cleared. Median size of the remaining partially cleared lesions decreased by 42.9%. The first SDL-PDT was pain-free for 7 patients (58.3%, VAS=0). Median VAS during and after the first treatment was 0 (0.0-0.3). For the second SDL-PDT, median VAS was 0.1 (0.0-5.5, during) and 0 (0.0-4.5, after). Both SDL-PDTs were pain-free for 6 patients. CONCLUSION: SDL-PDT was effective and nearly pain-free, emphasizing its advantages and potential for common practice.

Bringing the gentle properties of daylight photodynamic therapy indoors: A systematic review of efficacy and safety.

Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX during its formation is almost painless and as effective. Recent studies suggest that this gentle simultaneous activation can be performed indoors by replacing daylight with a suitable light source. We aimed to systematically review efficacy and tolerability of indoor gentle PDT of AKs using various light sources. We systematically searched MEDLINE, Embase, and the Cochrane Library for clinical studies of treatment efficacy or adverse events. Indoor gentle PDT consists of application of methyl aminolevulinate or 5-aminolevulinic acid on the skin prior to long time illumination, starting no later than one hour after application. Fifteen studies met the selection criteria, enrolling 518 patients with more than 5,000 AKs undergoing indoor gentle PDT. The studies mainly included thin AKs comprised of 8 uncontrolled studies and 7 randomized controlled trials (RCT) of which 3 were designed as non-inferiority RCTs. Results from both controlled and uncontrolled trials indicated good treatment tolerability with very low pain scores like those of daylight PDT. Reduction of AK lesions 3 months after indoor gentle PDT in RCTs ranged from 52% to 79%, which is comparable to classic and daylight PDT. All 3 non-inferiority RCTs reported that indoor gentle PDT was non-inferior in terms of efficacy to classic PDT. The included studies used varying treatment protocols with different pretreatments, incubation time, light sources, and irradiation time. No standard protocol for indoor gentle PDT exists yet.