Red Light Photodynamic Therapy Research Articles

Pilot study utilizing short contact protocols for treatment of actinic keratoses (AK) with ALA gel-red light photodynamic therapy (PDT)

Background: Red light photodynamic therapy (PDT) is an effective option for actinic keratosis (AK) lesions. However, stinging pain during illumination limits utility. Objective: To compare three modified red-light PDT regimens (short incubation, whole-face application, no occlusion) and to determine whether these can reduce pain yet still provide significant AK lesion clearance. Methods: Patients in this randomized clinical trial (n = 30) were randomized into one of three groups [incubation with 10% ALA gel, illumination with red-light]: Group A: 10 min, 20 min (75 J/cm2); Group B: 20 min, 10 min (37 J/cm2); Group C: 1 hour, 10 min (37 J/cm2). Two PDT treatments were administered 8 weeks apart. Lesions were counted at each visit, and pain was recorded on a scale from 0 – 10. Results: Patients Groups A and B (shorter incubations) experienced significantly less pain during illumination than Group C. After one treatment, the AK lesion reduction in Group A (59%) was statistically non-inferior to Group C (43%), with a noninferiority margin of ±15%. Final lesion counts after two PDT treatments showed a reduction from baseline by 82% in Group C, 76% in Group A, and 74% in Group B. Groups A and B did not meet the statistical non-inferiority endpoint relative to Group C after two treatments. Limitations: Small sample size, which limited the ability to reach statistical significance after 2 PDT treatments. Conclusion: Two short/modified red light PDT regimens were essentially painless, and all three provided AK lesion clearances comparable to conventional regimens.

High efficacy of red light photodynamic therapy with 10 % aminolevulinic acid gel irrespective of the extent of keratinocyte atypia in actinic keratosis – exploratory post-hoc analysis of three pivotal phase III trials

BackgroundPrimary endpoints of clinical studies investigating treatments for actinic keratosis (AK) are mainly based on clinical evaluation, but a recent study showed that in AK, clinical classification according to Olsen and the extent of keratinocyte atypia do not necessarily correlate. The influence of the epidermal extent of atypia on treatment efficacy is usually not investigated and therefore remains largely unknown. ObjectiveTo evaluate whether the extent of keratinocyte atypia influences efficacy of photodynamic therapy (PDT) when treating AK. MethodsWe performed a post-hoc analysis of histological (keratinocyte intraepithelial neoplasia (KIN)), and clinical (Olsen) data of biopsied lesions of three pivotal studies evaluating PDT using 10 % aminolevulinic acid (ALA) gel or vehicle and narrow- or broad-spectrum red light lamps. ResultsOverall, 514 biopsied lesions were considered. Clearance rates after red light PDT with 10 % ALA gel were comparable for KIN I-III (88.2 %, 92.0 % and 87.9 %) and Olsen I-II lesions for any given lamp type. Generally, clearance rates were higher using narrow- compared to broad-spectrum lamps. For both lamp types, the variation in clearance rates from KIN I-III was low. Clearance was lower with vehicle. LimitationsVarying lesion numbers in the subgroups and a remaining risk of bias due to the biopsies are potential limitations. ConclusionOur results suggest that red light PDT with 10 % ALA gel is an effective treatment option for AK regardless of the extent of keratinocyte atypia.

Effective treatment of actinic keratosis on the hands with red light photodynamic therapy using BF-200 ALA

BackgroundAcral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. MethodsWe analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. Results24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. ConclusionThis subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

Long-Term Improvement of Different Types of Acne Vulgaris Using a Mild Photodynamic Therapy Protocol with BF-200 ALA Gel: A Series of Cases.

Background: Photodynamic therapy (PDT) can be a promising alternative for patients with acne vulgaris. Our study aimed to evaluate the efficacy and safety of red light photodynamic therapy with BF-200 ALA gel in the treatment of different types of acne vulgaris. Methods: We performed a retrospective, observational study of a series of 22 cases. All patients were treated according to a mild PDT protocol. After a careful wash of the affected skin areas, BF-200 ALA gel was applied to the skin in a thin layer and incubated for 30 min, followed by illumination using narrow-spectrum red light (635 nm) at a dose of 4 J/cm2. Most patients received one (36.4%), two (27.3%), or three (22.7%) PDT sessions. About a third of the patients received concomitant acne treatment with topical retinoids. Results: Patients of 25.1 ± 8.9 years suffering from papulopustular (45.5%), nodular (27.3%), and comedonal acne (27.3%) in the face were included. Irrespective of acne type or severity, 95.5% of patients had good or excellent responses to the treatment with PDT (≥60% lesion clearance). We found no association between concomitant acne medication and the favorable results achieved by PDT. Most patients reported no adverse events (72.7%), except for six patients who experienced erythema. The good efficacy results were maintained over a follow-up period of 12.5 ± 10.8 months. Conclusions: In this study, we show that PDT with BF-200 ALA gel and low light dose is an effective and long-lasting option for the treatment of different acne types.

Exploring Patient Pain Experiences during and after Conventional Red Light and Simulated Daylight Photodynamic Therapy for Actinic Keratosis: A Qualitative Interview Study.

Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.

A dipyridophenazine Ni(II) dithiolene complex as a dual-acting cancer phototherapy agent activatable within the phototherapeutic window

A combination of photodynamic therapy (PDT) and photothermal therapy (PTT) within the phototherapeutic window (600–900 nm) can lead to significantly enhanced therapeutic outcomes, surpassing the efficacy observed with PDT or PTT alone in cancer phototherapy. Herein, we report a novel small-molecule mixed-ligand Ni(II)-dithiolene complex (Ni-TDD) with a dipyridophenazine ligand, demonstrating potent red-light PDT and significant near-infrared (NIR) light mild-temperature PTT activity against cancer cells and 3D multicellular tumour spheroids (MCTSs). The four-coordinate square planar complex exhibited a moderately intense absorption band (ε ∼ 3700 M−1cm−1) centered around 900 nm and demonstrated excellent dark and photostability in an aqueous phase. Ni-TDD induced a potent red-light (600–720 nm) PDT effect on HeLa cancer cells (IC50 = 1.8 μM, photo irritation factor = 44), triggering apoptotic cell death through efficient singlet oxygen generation. Ni-TDD showed a significant intercalative binding affinity towards double-helical calf thymus DNA, resulting in a binding constant (Kb) ∼ 106 M−1. The complex induced mild hyperthermia and exerted a significant mild-temperature PTT effect on MDA-MB-231 cancer cells upon irradiation with 808 nm NIR light. Simultaneous irradiation of Ni-TDD-treated HeLa MCTSs with red and NIR light led to a remarkable synergistic inhibition of growth, exceeding the effects of individual irradiation, through the generation of singlet oxygen and mild hyperthermia. Ni-TDD displayed minimal toxicity towards non-cancerous HPL1D and L929 cells, even at high micromolar concentrations. This is the first report of a Ni(II) complex demonstrating red-light PDT activity and the first example of a first-row transition metal complex exhibiting combined PDT and PTT effects within the clinically relevant phototherapeutic window. Our findings pave the way for designing and developing metal-dithiolene complexes as dual-acting cancer phototherapy agents using long wavelength light for treating solid tumors.

Cobalt(III) dibromo-BODIPY-8-hydroxyquinolinate for mitochondria-targeted red light photodynamic therapy

The photophysical properties of boron-dipyrromethene (BODIPY) dyes have made them suitable for cellular imaging and photodynamic therapy (PDT). The efficacy of these dyes can be augmented by designing their dibromo/diiodo derivatives. Heteroleptic Co(III) complexes of a tetradentate N,N,N,O-donor polypyridyl phenolate (HL) and bidentate N,O-donor 8-hydroxyquinoline (HL1) and its BODIPY (HL2) or dibromo-BODIPY (HL3) pendants, [CoIII(L)(L1−3)]X (1–3) (where X = ClO4 for 1, 2 and Cl for 3) were synthesized and studied. The dibromo-BODIPY ligand HL3 was structurally characterized. The dibromo-BODIPY complex 3, showing singlet oxygen quantum yield (ϕΔ) value of ∼0.25, displayed remarkable apoptotic photo-cytotoxicity in HeLa cancer cells upon red light (600–720 nm) irradiation giving half-maximal inhibitory concentration (IC50) value of 0.36 μM (photocytotoxicity index: >277). It was less toxic in normal cells. Cellular imaging studies revealed mitochondrial colocalization. This work exemplifies Co(III)–dibromo-BODIPY complex as a new class of metal-based PDT agent with higher efficacy than the dyes alone.

Lysosome directed red light photodynamic therapy using glycosylated iron-(III) conjugates of boron-dipyrromethene

To overcome the drawbacks associated with chemotherapeutic and porphyrin-based photodynamic therapy (PDT) agents, the use of BODIPY (boron-dipyrromethene) scaffold has gained prominence in designing a new generation of photosensitizers-cum-cellular imaging agents. However, their poor cell permeability and limited solubility in aqueous medium inhibits the in-vitro application of their organic form. This necessitates the development of metal-BODIPY conjugates with improved physiological stability and enhanced therapeutic efficacy. We have designed two iron(III)-BODIPY conjugates, [Fe(L1/2)(L3)Cl] derived from benzyl-dipicolylamine and its glycosylated analogue along with a BODIPY-tagged catecholate. The complexes showed intense absorption bands (ε ∼ 55,000 M−1 cm−1) and demonstrated apoptotic PDT activity upon red-light irradiation (30 J/cm2, 600–720 nm). The complex with singlet oxygen quantum yield value of ∼0.34 gave sub-micromolar IC50 (half-maximal inhibitory concentration) value (∼0.08 μM) in both HeLa and H1299 cancer cells with a photocytotoxicity index value of >1200. Both the complexes were found to have significantly lower cytotoxic effects in non-cancerous HPL1D (human peripheral lung epithelial) cells. Singlet oxygen was determined to be the prime reactive oxygen species (ROS) responsible for cell damage from pUC19 DNA photo-cleavage studies, 1,3-diphenylisobenzofuran and SOSG (Singlet Oxygen Sensor Green) assays. Cellular imaging studies showed excellent fluorescence from complex 2 within 4 h, with localization in lysosomes. Significant drug accumulation into the core of 3D multicellular tumor spheroids was observed within 8 h from intense in-vitro emission. The complexes exemplify iron-based targeted PDT agents and show promising results as potential transition metal-based drugs for ROS mediated red light photocytotoxicity with low dosage requirement.

Long-term follow up of ALA 10% gel and red-light photodynamic therapy for the treatment of squamous cell carcinoma in situ.

Photodynamic Therapy (PDT) with 10% aminolevulinic acid (ALA) gel and narrow-band red light has been previously shown to be safe and effective for the treatment of squamous cell carcinoma in situ (SCCis) on the trunk and extremities. However, there is a paucity of data in the literature evaluating long-term disease recurrence after PDT. Hence, we performed a follow-up study in which nine of the original twelve patients from our pilot study returned 29-40 months after their last PDT treatment. All patients were clinically clear of disease and only one of seven patients biopsied had residual disease, indicating a long-term clearance rate of 88%. Cosmetic outcomes and patient satisfaction were favorable. Our data supports that red-light PDT with 10% ALA gel can achieve long-term clinical and histopathologic disease clearance and is a viable alternative to surgery for select SCCis.

Efficacy of red-light photodynamic therapy with 10% ALA gel in relation to the epidermal extent of atypical keratinocytes in actinic keratosis - Retrospective exploratory analysis of three pivotal phase III trials

Efficacy of red-light photodynamic therapy with 10% ALA gel in relation to the epidermal extent of atypical keratinocytes in actinic keratosis - Retrospective exploratory analysis of three pivotal phase III trials

Long-term Follow Up of ALA 10% Gel and Red-Light Photodynamic Therapy for the Treatment of Squamous Cell Carcinoma In Situ

Long-term Follow Up of ALA 10% Gel and Red-Light Photodynamic Therapy for the Treatment of Squamous Cell Carcinoma In Situ

Successful treatment of Old World cutaneous leishmaniasis with red or green light photodynamic therapy

Cutaneous leishmaniasis is one of the most common travel dermatoses in Germany, which can be acquired not only in Africa, Asia or the American continent, but also in southern European countries. In addition to the currently available topical and systemic therapy options, there have been increasing reports of successful treatment of cutaneous leishmaniasis with photodynamic therapy (PDT) using numerous therapy regimens and different photosensitizers in recent years. We report on successful photodynamic therapy of Old World cutaneous leishmaniasis with red and green light PDT with 10% 5‑aminolevulinic acid.

Diffuse Optical Spectroscopy Monitoring of Experimental Tumor Oxygenation after Red and Blue Light Photodynamic Therapy

Photodynamic therapy (PDT) is an effective technique for cancer treatment based on photoactivation of photosensitizer accumulated in pathological tissues resulting in singlet oxygen production. Employment of red (660 nm) or blue (405 nm) light differing in typical penetration depth within the tissue for PDT performance provides wide opportunities for improving PDT protocols. Oxygenation dynamics in the treated area can be monitored using diffuse optical spectroscopy (DOS) which allows evaluating tumor response to treatment. In this study, we report on monitoring oxygenation dynamics in experimental tumors after PDT treatment with chlorin-based photosensitizers using red or blue light. The untreated and red light PDT groups demonstrate a gradual decrease in tumor oxygen saturation during the 7-day observation period, however, the reason is different: in the untreated group, the effect is explained by the excessive tumor growth, while in the PDT group, the effect is caused by the blood flow arrest preventing delivery of oxygenated blood to the tumor. The blue light PDT procedure, on the contrary, demonstrates the preservation of the blood oxygen saturation in the tumor during the entire observation period due to superficial action of the blue-light PDT and weaker tumor growth inhibition. Irradiation-only regimes show a primarily insignificant decrease in tumor oxygen saturation owing to partial inhibition of tumor growth. The DOS observations are interpreted based on histology analysis.

Optimizing treatment of acne with photodynamic therapy (PDT) to achieve long-term remission and reduce side effects. A prospective randomized controlled trial.

Photodynamic therapy with methyl aminolevulinate (MAL-PDT) is an effective treatment of acne vulgaris, but is associated with side effects. We performed a prospective randomized split-face study aimed at optimizing MAL-PDT treatment. Patients (n=33) were randomized to two or four treatments of PDT with MAL on one cheek and placebo vehicle on the other cheek, 1-2weeks apart. A 1.5-h pre-treatment with the MAL cream was followed by illumination with red light (20J/cm2). Assessments were performed before treatment and 4, 10, and 20weeks after the last treatment. In comparison to baseline, the number of inflammatory lesions at 20weeks on cheeks treated with MAL-PDT showed a relative decrease of 74% in the group with two treatments and 85% in the group with four treatments. This new treatment regimen for both MAL-PDT and red-light-only PDT, with shortened pre-treatment and reduced light dose, could be an effective modality.

Field cancerization treatment: Adjustments to an ALA red light photodynamic therapy protocol to improve pain tolerance

BackgroundField cancerization (FC) is described as an area with multiple actinic keratosis (AK) in an actinic damaged skin that requires treatment. Photodynamic therapy (PDT) is a treatment option, however, long drug light intervals (DLI) and pain during the illumination remain a challenge ObjectivePain and the efficacy of changes in DLI and illumination during PDT treatment for FC were evaluated MethodsThirty patients with widespread AK of upper limbs were selected. A 20% aminolevulinic acid (ALA) cream was applied on both forearms and hands after a light curettage. Three groups were evaluated: G1 (3 h of DLI); G2 (1.5 h of DLI); and, G3 (1.5 h of DLI with two-minutes pauses every 10 min during illumination). The limbs were treated with a LED prototype at 630 nm (36 J/cm2 of fluence in 40 min of irradiation). The pain score during illumination was evaluated with a numeric scale (from 0 to 10) and pain was defined as low (0–3), moderate (4-6), and severe (7-10). The AK counting was clinically performed before and 30 days after PDT. Significance between groups was tested using ANOVA single factor. ResultsA mean reduction in AK number of 56% in G1, 55% in G2, and 66% in G3 were observed, with no statistical significance. The comparison pain among the groups showed best results for G3 (p < 0,05). ConclusionUsing paused illumination and 1.5 h of DLI was possible to improve tolerance maintaining the clearance in red light ALA - PDT treatment.

Photodynamic therapy utilizing 10% ALA nano-emulsion gel and red-light for the treatment of squamous cell carcinoma in-situ on the trunk and extremities: Pilot study and literature update

BackgroundData evaluating the effectiveness of photodynamic therapy (PDT) with aminolevulinic acid (ALA) 10% nanoemulsion gel and red-light LED lamp for the treatment of squamous cell carcinoma in situ (SCCis) on the trunk and extremities is limited. Our study sought to investigate the safety and efficacy of utilizing ALA 10% gel with red-light lamp for the treatment of SCCis on the trunk and extremities. MethodsA single center prospective study of 12 patients with biopsy proven SCCis underwent one or two cycles of red-light PDT with ALA 10 % gel and 3 hours incubation period. Each cycle consisted of two treatments approximately 10 days apart. All participants had a biopsy for histologic evaluation 4 weeks following the last treatment. ResultsAll patients achieved clinical and histologic clearance following either one or two cycles at the 4-week post treatment follow up period. The majority of lesions were located on the extremities (n=10) with the remainder located on the trunk (n=2). The mean diameter of the lesions was 1.83 cm. Mild pain was noted in patients, with no interruption of treatment. ConclusionsOur study indicates that ALA 10% gel with a red-light lamp is a safe and effective treatment option for SCCis on the trunk and extremities.

Red light photodynamic therapy with BF-200 ALA showed superior efficacy in the treatment of actinic keratosis on the extremities, trunk, and neck in a vehicle-controlled phase III study

Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face. To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT). This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded. BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P<.0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P<.0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P=.0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT. Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK. BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated.

Pulsed Dye Laser-mediated Photodynamic Therapy is Less Effective than Conventional Photodynamic Therapy for Actinic Field Cancerization: A Randomized Half-side Comparative Study.

Previous research presents pulsed dye laser-mediated photodynamic therapy as a promising alternative to conventional red-light photodynamic therapy. In this study, 60 patients with 2 or more actinic keratoses randomly received either of these treatments on each side of the head. A physician blinded to the treatment evaluated treatment response at 6 months for each lesion, as completely, partially or not healed. Significantly lower complete clearance rates (10.3% vs 44.9%) and lesion-specific complete clearance rates were found for pulsed dye laser-mediated photodynamic therapy (47.9%) vs conventional red-light photodynamic therapy (73.4%). Significantly lower pain scores were found for pulsed dye laser-mediated photodynamic therapy, with a mean numerical rating of 2.3, compared with 4.1 for conventional red-light photodynamic therapy. The study population had a mean of 7.9 lesions, and 78% of patients had been treated previously for actinic keratoses on the treatment area. To conclude, in a population with severe sun damage, pulsed dye laser-mediated photodynamic therapy seems less effective than conventional red-light photodynamic therapy. Pulsed dye laser-mediated photodynamic therapy may still be a treatment option for patients who are not compliant with conventional redlight photodynamic therapy.

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer.

.Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient.Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall.Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer’s specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram.Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties.Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer’s specific uptake ratio.

Photodynamic therapy does not induce cyclobutane pyrimidine dimers in the presence of melanin.

Photodynamic therapy (PDT) is an office-based treatment for precancerous and early cancerous skin changes. PDT induces cell death through the production of reactive oxygen species (ROS). Cyclobutane pyrimidine dimers (CPDs) are the most important DNA changes responsible for ultraviolet (UV) carcinogenesis. Recently ROS induced by UVA were shown to generate CPDs via activating melanin. This raised the possibility that PDT induced ROS may also induce CPDs and mutagenesis in melanin containing cells. Previously the effect of PDT on CPDs in melanin containing cells has not been assessed. Our current work aimed to compare the generation of CPDs in melanin containing cells subjected to UVA treatment and porfimer sodium red light PDT. We used ELISA to detect CPDs. After UVA we found a dose dependent increase in CPDs in melanoma cells (B16-F10, MNT-1) with CPD levels peaking hours after discontinuation of UVA treatment. This indicated the generation of UVA induced dark-CPDs in the model. Nevertheless, PDT in biologically relevant doses was unable to induce CPDs. Our work provides evidence for the lack of CPD generation by PDT in melanin containing cells.