Blue Light Photodynamic Therapy Research Articles

Blue light aminolevulinic acid photodynamic therapy downregulates cell division and proliferation pathways in cutaneous squamous cell carcinoma.

5-Aminolevulinic acid (5-ALA) photodynamic therapy (PDT) is a treatment for actinic keratosis (AK) and has been studied as a treatment for noninvasive cutaneous squamous cell carcinoma (cSCC). PDT induces apoptosis and necrosis in AKs and cSCC. 5-ALA blue light PDT may modulate gene expression and pathways in surviving cells. In this study, differential gene expression and pathway analysis of cSCC and human dermal fibroblasts were compared before and after 5-ALA blue light PDT using RNA sequencing. No genes were differentially expressed after correcting for multiple testing (false discovery rate < 0.05). As a result, transcription factor, gene enrichment, and pathway analysis were performed with genes identified before multiple testing (p < 0.05). Pathways associated with proliferation and carcinogenesis were downregulated. These findings using 5-ALA blue light PDT are similar to previously published studies using methyl-aminolevulinic and red light protocols, indicating that surviving residual cells may undergo changes consistent with a less aggressive cancerous phenotype.

Photodynamic therapy for Cutibacterium acnes decolonization of the shoulder dermis

Introduction Cutibacterium acnes (C. acnes) is a common source of infection in shoulder surgery. 5-Aminolevulinic acid (5-ALA) is a naturally occurring metabolite of C. acnes that creates an exothermic reaction when activated by blue light. The purpose of this study was to evaluate the efficacy of preoperative photodynamic therapy using topical 5-ALA to decrease C. acnes colonization. Methods Patients were randomized to receive topical 5-ALA skin solution activated by blue light photodynamic therapy or standard of care preoperative skin preparation. Prior to skin incision, two punch biopsy specimens were taken from the portal sites and were incubated for 13 days. Culture positivity rate, days until positive, and semiquantitative growth classification were analyzed. Results Fifty patients undergoing arthroscopic shoulder surgery were randomized. The overall positive culture rate was 54%. All cultures were positive for C. acnes except for one. Sixty-four percent of standard preparation patients and 44% of investigational group patients had at least one positive culture for C. acnes. There was no significant difference between groups in patients with at least one positive C. acnes culture ( p = 0.49). Conclusion The use of photodynamic therapy undergoing arthroscopic shoulder surgery did not significantly reduce colonization of C. acnes as compared to standard preparation. Level of Evidence Level II.

Anticandidal Efficacy of Erythrosine with Nano-TiO2 and Blue LED-Mediated Photodynamic Therapy against Candida albicans Biofilms on Acrylic Resin: A Preliminary Study.

Incorporating an enhancer such as nano-titanium dioxide into antimicrobial photodynamic therapy can improve treatment outcome.This study aimed to compare the anticandidal efficacy of photodynamic therapy by erythrosine with nano-titanium dioxide (nano-TiO2) stimulated by a blue light emitting diode with three standard dental antifungal agents. Candida albicans biofilms on acrylic resin plates were treated for 15 minutes with either nystatin, fluconazole, Polident, 220µM erythrosine + 1% (w/w) nano-TiO2 + 15 J/cm2 blue light photodynamic therapy (Ery PDT), or distilled water. For the Ery PDT group, blue light was applied for 1 minute after incubation. After 1, 3, and 6 hours, the colony forming units in log10 (log10CFU/mL) were compared. The ultrastructure of C. albicans on the acrylic resin plates treated with erythrosine + nano-TiO2 + blue light was examined using transmission electron microscopy at magnification of 30,000x. After 1 hour, nystatin, Polident, and Ery PDT indifferently inhibited C. albicans. At 6 hours, Ery PDT reduced the number of viable C. albicans in biofilms by 0.28log10 CFU/mL, which was equal to the effect of fluconazole and Polident. Transmission electron microscopy demonstrated that Ery PDT altered the C. albicans cell morphology by inducing cell wall/membrane rupture. Photodynamic therapy with erythrosine + nano-TiO2 + blue light at low light power density (15 J/cm2) was as effective at inhibiting C. albicans biofilm on acrylic resin as fluconazole and Polident.

Study of hematoporphyrin monomethyl ether-mediated blue-light photodynamic therapy in the treatment of oral ulcers infected with Staphylococcus aureus: In vivo evaluation.

Clinical suppurative infection is mainly caused by Staphylococcus aureus. Although many antibiotics can be used to kill S. aureus, the resulting resistance problem is difficult to solve. Therefore, it is necessary to seek a new sterilizing method to solve the problem of drug resistance of S. aureus and improve the therapeutic effect of infectious diseases. Photodynamic therapy (PDT) has become an alternative for the treatment of a variety of drug-resistant infectious diseases due to its advantages of non-invasive, specific targeting, and no drug resistance. We have confirmed the advantages and experimental parameters of blue-light PDT sterilization in vitro experiments. This study aimed to treat buccal mucosa ulcer of hamster infected with S. aureus according to the parameters obtained in vitro experiment, and observe the bactericidal effect of hematoporphyrin monomethyl ether (HMME) mediated blue-light PDT in vivo and its therapeutic effect on tissue infection. The results indicated that HMME mediated blue-light PDT can effectively kill S. aureus in vivo and promote the healing of the oral infectious wound.The study findings lay a foundation for carrying out more HMME mediated blue-light PDT sterilizing therapy.

Low curcumin concentrations combined with blue light inhibits cutibacterium acnes biofilm-induced inflammatory response through suppressing MAPK and NF-κB in keratinocytes

BackgroundCurcumin has been employed as a photosensitizer agent during photodynamic therapy (PDT). Cutibacterium acnes (C. acnes) can cause an inflammatory response in human keratinocytes; however, no research has been conducted to determine whether curcumin and its photodynamic properties can prevent this inflammatory reaction. ObjectiveWe hypothesized that curcumin may control the C. acnes biofilm-induced inflammatory response in keratinocytes, either alone or in combination with blue light photodynamic therapy. MethodsFollowing C. acnes biofilm stimulation, human primary keratinocytes were treated with 20 μM curcumin solution alone or 5 μM curcumin with combined blue light irradiation. The amount of secreted protein was measured using an ELISA kit. The expression levels of Toll-like receptor 2 (TLR2) and its downstream proteins were determined using western blot. ResultsTreatment with 20 μM curcumin, but not 5 μM curcumin, reduced the inflammatory response to C. acnes biofilms in keratinocytes by blocking the TLR2/MAPK/NF-κB pathway. Interestingly, 5 μM curcumin combined with blue light also reduced the C. acnes biofilm-induced inflammation indicated above by blocking the TLR2/MAPK/NF-κB pathway. ConclusionCurcumin alone, in sufficient concentrations, or low-concentration curcumin with blue light had anti-inflammatory activity on keratinocytes stimulated by C. acnes biofilms through inhibition of MAPK and NF-κB signaling pathways by downregulating TLR2 expression.

283 Photodynamic therapy for basal cell carcinoma enhanced by pretreatment with oral vitamin D: interim results of a prospective clinical trial

Photodynamic therapy (PDT) is used in Europe to treat basal cell carcinoma (BCC), but it is not approved in the USA due to uncertainties about efficacy. Vitamin D3 (VD3; cholecalciferol) treatment prior to PDT improves BCC responses in mice. A prospective, double-blind, crossover clinical trial [NCT03467789] was designed to test whether oral VD3 pretreatment enhances BCC response to blue light PDT. Participants received 3 PDT treatments (20% ALA, 4 h; 417 nm, 30 min) 2 months apart. High-dose VD3 or placebo was administered prior to each of the first two PDT sessions.

Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial

In mouse models of skin cancer, high-dose oral vitamin D3 (VD3; cholecalciferol) combined with photodynamic therapy (PDT) can improve the clearance of squamous precancers (actinic keratoses [AKs]). To determine whether oral VD3 can improve the clinical efficacy of a painless PDT regimen in humans with AK. The baseline lesion counts and serum 25-hydroxyvitamin D3 levels were determined. In group 1, 29 patients underwent gentle debridement and 15-minute aminolevulinic acid preincubation with blue light (30minutes; 20J/cm2). In group 2, 29 patients took oral VD3 (10,000 IU daily for 5 or 14days) prior to debridement and PDT. Lesion clearance was assessed at 3 to 6months. In group 1, the mean clearance rates of facial AK were lower in patients with VD3 deficiency (25-hydroxyvitamin D3 level < 31ng/dL; clearance rate, 40.9%±42%) than in patients with normal 25-hydroxyvitamin D3 levels (62.6%±14.2%). High-dose VD3 supplementation (group 2) significantly improved the overall AK lesion response (72.5%±13.6%) compared with that in group 1 (54.4%±22.8%). No differences in side effects were noted. Nonrandomized trial design (interventional cohort matched to registry-based controls). Oral VD3 pretreatment significantly improves AK clinical responses to PDT. The regimen appears promising and well tolerated.

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.

Blue light photodynamic therapy with 5-aminolevulinic acid in refractory mycosis fungoides: A prospective, open-label study

Blue light photodynamic therapy with 5-aminolevulinic acid in refractory mycosis fungoides: A prospective, open-label study

Photodynamic Therapy in Refractory Mycosis Fungoides: A Prospective, Open-Label Study

Background:Case reports suggest photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an effective treatment for refractory mycosis fungoides (MF). No prospective trials have examined the use of ALA-PDT in MF. Objective:We aimed to assess the efficacy of ALA-PDT in refractory MF. Methods:This was a prospective study at Mayo Clinic in Scottsdale, Arizona in patients ≥ 18 years with plaque-stage treatment-refractory MF. Monthly sessions of ALA with blue light PDT were administered for up to six months. Responses were measured by Composite Assessment of Index Lesion Severity (CAILS) and Physician Global Assessment (PGA). Ad hoc analysis with modified CAILS (mCAILS) was performed, eliminating hyperpigmentation from scoring. Results:Eleven patients (30 total lesions) were treated. Six patients completed the trial per protocol. Objective response rates were 36.4% by PGA (10.9-69.2%), 18.2% by CAILS (2.3-51.8%), and 36.4% by mCAILS (10.9-69.2%). Limitations:Five patients did not complete all six PDT cycles per protocol, possibly accounting for reduced efficacy. Conclusion:ALA-PDT with blue light irradiation was moderately effective and well tolerated in refractory plaque stage MF. Lower response rates compared to similar trials may be partially explained by utilization of strict lesional assessment criteria and other variations in methodology. Disclosures Mangold: MiRagen:Research Funding;Sun Pharma:Research Funding;Elorac:Research Funding;Kirin:Membership on an entity's Board of Directors or advisory committees;Solagenix:Research Funding. OffLabel Disclosure: Photodynamic therapy is a two-step therapy in which a drug that acts as a photosensitizer is administered to target a diseased tissue, followed by illumination with visible light to activate the drug and destroy the target tissue. PDT has been used to treat internal cancers as well as treatment of cancer and precancer of the skin.

A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination

Bluelight photodynamic therapy (PDT) is effective for actinic keratosis, but many patients experience stinging pain during illumination. To compare a conventional regimen (1hour of 5-aminolevulinic acid [ALA] preincubation, followed by blue light) versus a new modified regimen in which blue light is started immediately after ALA application. A clinical trial with a bilaterally controlled, intrapatient study design was conducted with 23 patients. Topical 20% ALA was applied to the entire face and/or scalp. On 1 side of the body, blue light was started immediately and continued for either 30, 45, or 60minutes (simultaneous PDT). On the contralateral side, the blue light began 1hour after ALA application and lasted 1000seconds (conventional PDT). Pain was evaluated on a scale from 0 to 10. Actinic keratosis lesion counts were determined by clinical examination and photography. All patients experienced significantly less pain during simultaneous illumination than during the conventional regimen. At 3months after treatment, lesion clearance was nearly identical on the 2 sides, as determined by statistical testing of noninferiority ± 15% margin. Although bilaterally controlled, the study was relatively small. Additional studies are recommended. The modified PDT regimen is essentially painless, yet it provides treatment efficacy similar to a conventional regimen.

Bactericidal effects of hematoporphyrin monomethyl ether-mediated blue-light photodynamic therapy against Staphylococcus aureus.

The implementation of photodynamic therapy (PDT) usually uses red light as the excitation source to obtain a deeper penetration depth. However, for some superficial infectious diseases, using red-light PDT may damage the normal tissues underneath. If we choose a shorter wavelength light, then the effect of PDT can be limited to the superficial region. This study assessed the effect of blue-light PDT against Staphylococcus aureus. The absorption of hematoporphyrin monomethyl ether (HMME) by S. aureus was investigated using fluorescence spectroscopy. The bactericidal effects of HMME, light alone, and PDT using blue light (405 nm) on S. aureus were studied. The results indicate that the HMME uptake by S. aureus rapidly reached a certain value, then steadily increased with time in the range of 0-80 min, and thenreached a plateau at 80 min before a slow decline afterward. Without light irradiation, less than 2 μg ml-1 HMME showed no bactericidal effect on S. aureus. Without HMME, blue-light at a power density of 20 mW cm-2 had no significant bactericidal effect for 0.5 min to 10 min. When 2 μg ml-1 of HMME was combined with blue-light (20 mW cm-2), the bactericidal effect showed a reduction of 3 log10 with the extension of irradiation time. These results demonstrated that bacteria have the ability to absorb HMME, and HMME-mediated blue-light PDT can effectively kill the bacteria, which laid the foundation for blue-light PDT as a non-invasive treatment for superficial infectious diseases.

Blue light versus red light for photodynamic therapy of basal cell carcinoma in patients with Gorlin syndrome: A bilaterally controlled comparison study

Photodynamic therapy (PDT) is a non-scarring alternative for treating basal cell carcinoma (BCC) in patients with Basal Cell Nevus Syndrome (BCNS), also known as Gorlin syndrome. In Europe, red light (635 nm) is the predominant source for PDT, whereas in the United States blue light (400 nm) is more widely available. The objective of this study was to conduct a head-to-head comparison of blue light and red light PDT in the same BCNS patients. In a pilot study of three patients with 141 BCC lesions, 5-aminolevulinate (20% solution) was applied to all tumors. After 4 h, half of the tumors were illuminated with blue light and the remainder with red light. To ensure safety while treating this many tumors simultaneously, light doses were escalated gradually. Six treatments were administered in three biweekly sessions over 4 months, with a final evaluation at 6 months. Tumor status was documented with high-resolution photographs. Persistent lesions were biopsied at 6 months. Clearance rates after blue light (98%) were slightly better than after red light (93%), with blue light shown to be statistically non-inferior to red light. Eight suspicious lesions were biopsied, 5 after red light (5/5 were BCC) and 3 after blue light (1 was BCC). Blue light PDT was reportedly less painful. Blue light and red light PDT appear to be equally safe and perhaps equally effective for treating BCC tumors in BCNS patients. Further studies to evaluate long-term clearance after blue light PDT are needed.

Singlet Oxygen Production and Biological Activity of Hexanuclear Chalcocyanide Rhenium Cluster Complexes [{Re6Q8}(CN)6]4– (Q = S, Se, Te)

Octahedral rhenium cluster complexes have recently emerged as relevant building blocks for the design of singlet oxygen photosensitizing materials toward biological applications such as blue-light photodynamic therapy. However, their singlet oxygen generation ability as well as biological properties have been studied only superficially. Herein we investigate in detail the singlet oxygen photogeneration, dark and photoinduced cytotoxicity, cellular uptake kinetics, cellular localization and in vitro photoinduced oxidative stress, and photodynamic cytotoxicity of the series of octahedral rhenium cluster complexes [{Re6Q8}(CN)6]4-, where Q = S, Se, Te. Our results demonstrate that the selenium-containing complex possesses optimal properties in terms of absorption and singlet oxygen productivity. These features coupled with the cellular internalization and low dark toxicity lead to the first photoinduced cytotoxic effect observed for a molecular [{M6Q8}L6] complex, making it a promising object for further study in terms of blue-light PDT.

Randomized, Controlled Trial of Fractional Carbon Dioxide Laser Resurfacing Followed by Ultrashort Incubation Aminolevulinic Acid Blue Light Photodynamic Therapy for Actinic Keratosis

Aminolevulinic acid (ALA) photodynamic therapy (PDT) is an established treatment option for actinic keratosis (AK), and recently fractional carbon dioxide (CO2) laser was shown to improve outcomes; but studies of short incubation photosensitizer are lacking. Assess the efficacy of short incubation ALA followed by blue light PDT with and without previous fractional CO2 treatment for the treatment of AK. Randomized, paired split-design, controlled trial of fractional CO2 followed by ultrashort 15-minute versus 30-minute incubation ALA and blue light PDT for the treatment of AK on the face. The complete clearance rates (CRs) at 8 weeks after ALA PDT with and without FxCO2 at 30- and 15-minute ALA incubation times were 89.78% (+FxCO2) versus 71.20% CR (-FxCO2) at 30', and 86.38% (+FxCO2) versus 69.23% (-FxCO2) at 15' ALA incubation. All lesion improvements were statistically significant. This randomized, comparative paired group controlled clinical study demonstrates that ultrashort 15- and 30-minute incubation ALA PDTs are of limited efficacy for the treatment of AK. Pretreatment with fractional ablative resurfacing yields statistically significant greater AK clearance with ALA-PDT at ultrashort ALA incubations followed by blue light.

Nano-curcumin influences blue light photodynamic therapy for restraining glioblastoma stem cells growth

Nano-curcumin based blue light photodynamic therapy has therapeutic potential in the arsenal of glioblastoma cancer stem cells recurrence.

Recent advances in acne pathogenesis: implications for therapy.

Acne pathogenesis is a multifactorial process that occurs at the level of the pilosebaceous unit. While acne was previously perceived as an infectious disease, recent data have clarified it as an inflammatory process in which Propionibacterium acnes and innate immunity play critical roles in propagating abnormal hyperkeratinization and inflammation. Alterations in sebum composition, and increased sensitivity to androgens, also play roles in the inflammatory process. A stepwise approach to acne management utilizes topical agents for mild to moderate acne (topical retinoid as mainstay ± topical antibiotics) and escalation to oral agents for more resistant cases (oral antibiotics or hormonal agents in conjunction with a topical retinoid or oral isotretinoin alone for severe acne). Concerns over antibiotic resistance and the safety issues associated with isotretinoin have prompted further research into alternative medications and devices for the treatment of acne. Radiofrequency, laser, and light treatments have demonstrated modest improvement for inflammatory acne (with blue-light photodynamic therapy being the only US FDA-approved treatment). However, limitations in study design and patient follow-up render these modalities as adjuncts rather than standalone options. This review will update readers on the latest advancements in our understanding of acne pathogenesis and treatment, with emphasis on emerging treatment options that can help improve patient outcomes.

Effective blue light photodynamic therapy does not affect cutaneous langerhans cell number or oxidatively damage DNA.

Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin. Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT. Customary blue light BASI-ALA-PDT does not affect the LC number or produce oxidative DNA damage, the sequelae of red light PDT responsible for immunosuppression in treated skin.

Treatment of Angiofibromas of Tuberous Sclerosis with 5-Aminolevulinic Acid Blue Light Photodynamic Therapy Followed by Immediate Pulsed Dye Laser

Treatment of Angiofibromas of Tuberous Sclerosis with 5-Aminolevulinic Acid Blue Light Photodynamic Therapy Followed by Immediate Pulsed Dye Laser

Treatment of Angiofibromas of Tuberous Sclerosis with 5-Aminolevulinic Acid Blue Light Photodynamic Therapy Followed by Immediate Pulsed Dye Laser

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