Light Source For Photodynamic Therapy Research Articles

Tumor microenvironment-modulated nanoparticles with cascade energy transfer as internal light sources for photodynamic therapy of deep-seated tumors

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.

The Potential of Narrow-Band Imaging as a Novel Light Source for Photodynamic Therapy for Superficial Cancers via Endoscopes.

Photodynamic therapy (PDT) has advanced through the utilization of photosensitizers and specific-wavelength light (≥ 600 nm). However, the widespread adoption of PDT is still impeded by high equipment costs and stringent laser safety requirements. Porphyrins, crucial in PDT, have another absorbance peak of blue light (λ = 380 - 500 nm). This peak corresponds to the wavelength of narrow-band imaging (NBI) (λ = 390 - 445 nm), an image-enhancement technology integrated into endoscopes by Olympus Medical Systems. The study aimed to investigate the potential of widely adopted NBI as a PDT light source for superficial cancers via endoscopes. Esophageal and biliary cancers were selected for investigation. Human esophageal cancer cell lines (KYSE30, KYSE70, KYSE170) and cholangiocarcinoma cell lines (HuCCT-1, KKU-213) were subjected to verteporfin-mediated PDT under NBI light (λ = 390 - 445 nm). Assessments included spectrometry, crystal violet staining, and fluorescein imaging of singlet oxygen generation and apoptosis. Verteporfin exhibited a peak (λ = 436 nm) consistent with the NBI spectrum, suggesting compatibility with NBI light. NBI light significantly inhibited the growth of esophageal and biliary cancer cells. The half-maximum effective concentration (EC50) values (5 J/cm2) for KYSE30, KYSE70, KYSE170, HuCCT-1, and KKU-213 were calculated as 2.78 ± 0.37µM, 1.76 ± 1.20 µM, 0.77 ± 0.16 µM, 0.65 ± 0.18 µM, and 0.32 ± 0.04 µM, respectively. Verteporfin accumulation in mitochondria, coupled with singlet oxygen generation and observed apoptotic changes, suggests effective PDT under NBI light. NBI is a promising PDT light source for superficial cancers via endoscopes.

Real-Time Monitoring of Colorectal Cancer Location and Lymph Node Metastasis and Photodynamic Therapy Using Fucoidan-Based Therapeutic Nanogel and Near-Infrared Fluorescence Diagnostic-Therapy System.

We report real-time monitoring of colorectal cancer, lymph node metastasis of colorectal cancer cells, and tumor growth inhibition through photodynamic therapy (PDT) using a near-infrared fluorescence diagnostic-therapy system with a light source for PDT and a fucoidan-based theranostic nanogel (CFN-gel) with good accumulation efficiency in cancer cells. To confirm the effect of the fabricated system and developed CFN-gel, in vitro and in vivo experiments were performed. Chlorin e6 (Ce6) and 5-aminolevulinic acid (5-ALA) were used for comparison. We confirmed that CFN-gel has a high accumulation efficiency in cancer cells and high fluorescence signals in near-infrared light for a long period, and only CFN-gel delayed the growth rate of cancer in terms of its size in PDT. In addition, using the near-infrared fluorescence diagnostic-therapy system and CFN-gel prepared for these experiments, the lymph node metastasis of cancer cells was imaged in real time, and the metastasis was confirmed through H&E staining. The possibility of image-guided surgery and identification of lymph node metastasis in colorectal cancer can be confirmed through CFN-gel and a near-infrared fluorescence diagnostic-therapy system that includes various light sources.

Effective fluence and dose at skin depth of daylight and lamp sources for PpIX-based photodynamic therapy.

Skin-based photodynamic therapy (PDT) is used for the clinical treatment of actinic keratosis (AKs) and other skin lesions with continued expansion into the standard of care. Due to the spectral dependency of photosensitizer activation and skin optical fluence, there is a need for more accurate methods to estimate the delivered dose at depth from different PDT light sources and treatment regimens. Develop radiometric methods for calculating photosensitizer-effective fluence and dose at depth and determine differences between red-lamp, blue-lamp, and daylight-based PDT treatments. Radiometric measurements of FDA-approved PDT lamp sources, outdoor daylight, and indoor daylight were performed for clinically relevant AK treatments. The protoporphyrin IX (PpIX) equivalent irradiance, fluence, and dose for each light source were calculated from the PpIX absorption spectrum and a 7-layer skin fluence model. The effective fluence and dose at depth was estimated by combining the spectral attenuation predicted at each wavelength and depth with the source fluence at each wavelength. The red-lamp source had the highest illuminance (112,000lumen/m2), but lowest PpIX-effective irradiance (9.6W/m2), and highest effective fluence at depth (10.8W/m2 at 500µm). In contrast, the blue light source had the lowest illuminance (2300lumen/m2), but highest PpIX effective irradiance (37.0W/m2), and ultimately the lowest effective fluence at depth (0.18W/cm2 at 500µm). The daylight source had values of (outdoor | indoor) illuminance of (49,200 | 37,800 lumen/m2), effective irradiance of (19.2 | 10.7W/m2), and effective fluence of (1.50 | 1.08W/m2 at 500µm). The effective fluence and dose at depth facilitated the comparison of treatment regimens, for example, calculating an equivalent dose for a 2 hr indoor daylight treatment and a 10min red-light treatment for the 300-1000μm depth range. The consideration of PpIX-effective fluence at varying depths is necessary to provide adequate comparisons of the delivered dose from PDT light sources. Methods for calculating radiometric fluence and delivered dose at depth were introduced, with open source MATLAB code, to help overcome the limitations of commonly used photometric and irradiance-based reporting.

Photodynamic therapy with light-emitting diode arrays producing different light fields induces apoptosis and necrosis in gastrointestinal cancer.

Light-emitting diodes (LEDs) have become a new light source for photodynamic therapy (PDT) because of their excellent optical properties, small size, and low cost. LED arrays have so far been designed to meet the need for accurate illumination of irregular lesions. However, LED arrays determine not only the shape of the illuminated spot but also the light field, which has a significant impact on the efficacy of PDT. We designed three types of LED arrays producing different light fields, namely an intensive LED array for a uniform light field, a sparse LED array for a non-uniform light field, and a point LED array for a Gaussian-like light field, and investigated the effect and mechanism of these light fields on PDT for gastrointestinal cancer both in vitro and in vivo. We found that intensive LED-PDT induced earlier and more serious cell death, including apoptosis and necrosis, than sparse LED-PDT and point LED-PDT. Among the three LED arrays, the intensive LED array induced cells to produce more differential proteins (DEPs), mainly related to mitochondria, ribosomes, and nucleic acids. DEPs in cells subjected to sparse LED- and point LED-PDT were mainly involved in extracellular activities. For MGC-803 tumor-bearing mice, intensive LED-PDT and point LED-PDT had better tumor ablation effect than sparse LED-PDT. Notably, recurrence was observed on day 7 after sparse LED-PDT. VCAM-1 and ICAM-1 were highly expressed in sparse LEDs-PDT treated tumor tissues and were associated tumor angiogenesis, which in turn lead to poor tumor suppression. Therefore, the type of LED array significantly affected the performance of PDT for gastrointestinal cancer. Uniform light field with low power densities work better than non-uniform and Gaussian-like light fields.

Special issue on enhanced photodynamic therapy: Part II

Special issue on enhanced photodynamic therapy: Part II

X-Ray Triggered Nanoscintillators Photosensitize Pancreatic Cancer and Stimulate a Robust Systemic Immune Response

<h3>Purpose/Objective(s)</h3> X-ray excited photodynamic therapy (XPDT) utilizes X-ray excited nano-scintillators as a light source for photodynamic therapy to treat solid tumors in deep tissues and stimulate immunogenic tumor necrosis. The goals of our study were twofold: (1) to assess the efficacy of a novel XPDT agent, pYSM, in enhancing the regression of murine pancreatic tumors using low doses of radiation, and (2) to evaluate the immunogenic effects of XPDT and immunotherapy in stimulating a systemic anti-tumor immune response. <h3>Materials/Methods</h3> pYSM was synthesized by coating Y₂O₃:Eu nanoparticles in a mesoporous silica shell before loading the shell with methylene blue dye as a photosensitizer and encapsulating the complex in polyethylene glycol to improve systemic circulation. The generation of reactive oxygen species from irradiating pYSM in solution was measured by a singlet oxygen sensor green (SOSG) assay. In vitro studies were conducted using Panc02, a murine pancreatic cell line, by culturing cells with pYSM and measuring the cell viability after irradiation. In vivo studies were performed using C57BL/6 mice with subcutaneous bilateral flank injections of Panc02 cells. A biodistribution assay was performed to confirm that the intravenous tail-vein injection of pYSM resulted in the accumulation of the XPDT agent within the tumor microenvironment. Only right-sided tumors were treated with either XPDT+immunotherapy, XPDT only, radiotherapy only, or pYSM only, and left-sided tumors were left untreated. Tumor growth delay curves were measured for both treated and untreated tumors, and flow cytometry was performed on both tumors to measure the immune response in all treatment groups. <h3>Results</h3> XPDT mediated by pYSM resulted in the greater generation of reactive oxygen species generation under a 10 Gy dose when compared to controls. And in vitro studies confirmed the greater cytotoxic effects of pYSM under X-ray irradiation as compared to controls. Additionally, in vivo studies showed the enhanced tumor regression of pYSM-mediated XPDT+immunotherapy as compared to controls in both right-sided (treated) and left-sided (untreated) tumors, suggesting an abscopal effect, as well as an increase in immune responses within the microenvironment of both right-sided and left-sided tumors. <h3>Conclusion</h3> pYSM is a novel, viable construct capable of performing XPDT to treat solid tumors. Additionally, XPDT mediated by pYSM combined with immunotherapy can generate a systemic anti-tumor immune response that leads to the regression of treated tumors as well as an abscopal effect. This combined treatment modality can be used to treat deep-seated solid tumors with poor immunogenic profiles.

Photoactivation of Chemotherapeutic Agents with Cerenkov Radiation for Chemo-Photodynamic Therapy.

Cerenkov radiation (CR) can be used as an internal light source in photodynamic therapy (PDT). Methotrexate (MTX) and paclitaxel (PTX), chemotherapeutic agents with wide clinical use, have characteristics of photosensitizers (PS). This work evaluates the possibility of photoexciting MTX and PTX with CR from 18F-FDG to produce reactive oxygen species (ROS) capable of inducing cytotoxicity. PTX did not produce ROS when excited by CR from 18F-FDG, so it is not useful for PDT. In contrast, MTX produces 1O2 (detected by ABMA) in amounts sufficient to significantly decrease the viability of the T47D cells. MTX solutions of 100 nM combined with 18F-FDG activities of 50 (1.85 MBq) and 100 μCi (3.7 MBq) produced a significant decrease in cell viability to (50.09 ± 4.95) and (47.96 ± 11.19)%, respectively, compared to MTX (66.29 ± 5.92)% and 18F-FDG (91.35 ± 7.00% for 50 μCi and 99.43 ± 11.03% for 100 μCi) alone. Using the CellRox Green reagent, the intracellular production of ROS was confirmed as the main mechanism of cytotoxicity. The results confirm the therapeutic potential of photoactivation with CR and the synergy of the combined treatment with chemotherapy + photodynamic therapy (CMT + PDT). The combination of chemotherapeutic agents with PS properties and β-emitting radiopharmaceuticals, previously approved for clinical use, will make it possible to shorten the evaluation stages of new CMT + PDT systems.

A covalent organic framework with a self-contained light source for photodynamic therapy.

External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host-guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by both H2O2-overexpressed 4T1 and H2O2-less expressed HCT116 and MCF-7 xenograft models.

Study of synergistic effects of Ficus Carica leaves extract mediated chemo-photodynamic therapy on rhabdomyosarcoma cells

BackgroundChemotherapy for rhabdomyosarcoma (RD) is effective, but it has critical side effects and unavoidable challenges. Photodynamic therapy (PDT) is an approach to treating cancer with relatively moderate side effects. Plant products are a rich source of polyphenols, which have potent antioxidant and anticancer activities. Therefore, their research has become an emerging field in recent decades. PurposeThis work aimed to evaluate the potential of hydrophobic extract of Ficus Carica (FC) to determine whether FC in the presence of low dose chemo and Aluminium Phthalocyanine (Photosense®) mediated photodynamic therapy synergistically enhances the treatment efficacy of RD cells. MethodFC with and without combination with individual therapeutic modalities like photosense mediated photodynamic therapy, chemotherapy, and their combinations were studied for cell viability and morphological changes in invitro RD cells. A semiconductor diode laser (630 nm) was used as a light source in PDT. The cytotoxic effect of FC on cell viability and cellular morphological changes were investigated by MTT reagent and a camera attached to an inverted visible light microscope. The effect of FC, followed by di-combination with low dose chemo (doxorubicin-HCl, and dacarbazine), Photosense® mediated PDT and chemo-Photosense® mediated PDT (tri-combination) at 630 nm diode laser and 10 J/cm2 fluency were also investigated by MTT reagent. The combination index method is used to identify the synergistic effect of combination therapy by using CompuSyn software based on the Chou-Talalay method. ResultsThe dose-dependent effect of FC on cell viability and cellular morphological changes were observed in the RD cell line. It was found that the pre incubation of FC potentiated the anticancer effect as a neoadjuvant agent for doxorubicin-HCl and decarbazine based chemotherapy, Photosense® mediated PDT and chemo-PDT (tri-combination) with synergistic effect (CI<1). ConclusionThese results suggest a possible thread that the low dose combination of the aforementioned therapeutic modalities in the presence of FC remarkably enhances the treatment efficacy of RD in comparison with a single-agent treatment modality. The proposed sequence of FC with chemo and PDT might present better therapeutic outcomes in RD therapies and may provide result for RD metastasis. FC may also be used in the application of phyto-PDT to cancer in the future.

Preliminary Monte Carlo simulation of non-laser light sources for photodynamic therapy

In photodynamic therapy (PDT), a photosensitizing agent is administered following irradiation on the target volume. The wavelength beam to activate the photosensitizer is ranging from 400 nm to 800 nm. Such wavelengths are generated by laser and non-laser light sources. However, the use of x-ray induced in photodynamic therapy has been investigated as a combination of radiotherapy and PDT. Moreover, x-rays are used for deeper penetration into tissue, extending the use of this therapy for tumours that would not be reachable by conventional PDT. In general, x-rays with keV to MeV energies are used for X-PDT. The aim of the present work is to investigate the use of monochromatic, low-energy beams for photodynamic therapy applications. Monte Carlo simulations are performed for distinct target volumes irradiated by a nonlaser (low-energy x-rays). Models of soft tissue and a mixture some photosensitizer plus soft tissue were considered. For each case, the energy fluence distribution at a given depth was calculated. A higher percentage difference of ∼20% was found when comparing the beam profile between soft tissue and the mixing Hpd, Photofrin, ALA, PpIX with soft tissue for low energy x-ray. Preliminary results showed that simulated x-ray beams could work for PDT.

Electron transfer reactions in rhodamine: Potential use in photodynamic therapy

Rhodamine (R) compounds are photosensitizers with low production of 1O2, so these compounds have not been considered very often for photodynamic therapy (PDT). Rhodamine-6G (R6G) undergoes electron transfer reactions with folic acid (FA). This reaction converts this form of R into a potential photosensitizer (PS) for PDT. The occurrence of this reaction with other R or oxygen has not yet been proven. The low penetrability of visible light into the skin has led to the proposal of a PDT light source alternative to Cerenkov radiation (CR). This work evaluates and compares the occurrence of type-I transfer reactions of R6G, R123, and RB with FA and oxygen when irradiated at 532 nm. The potential use of these compounds as type-I photosensitizers for PDT was also evaluated in vitro by excitation with CR. R electron transfer reactions with FA and oxygen were monitored by emission fluorescence and ultraviolet/visible (UV/Vis) absorption of 2,6-dichlorophenol-indophenol (DCPIP) as a redox indicator, respectively. 177Lu and 18F were used as CR sources. The results showed that the three R compounds underwent type-I transfer reactions with FA in the order R123 > R6G > RB when irradiated at 532 nm. Excitation of R6G using CR was demonstrated. Only R6G showed a type-I reaction with O2. By irradiating T47D tumor cells with a 532 nm laser light, cell death occurred in the order R6G>R123>RB. The same trend was found when cells were irradiated with CR. The possibility of using the type-I reaction between R compounds and biomolecules provides a new perspective in the use of these dyes in PDT.

In vitro irradiation of doxorubicin with 18F-FDG Cerenkov radiation and its potential application as a theragnostic system.

Doxorubicin (DOX), an effective chemotherapeutic agent, has a wide excitation band centred at 480 nm. Cerenkov radiation (CR) is considered an internal light source in photodynamic therapy (PDT). DOX could be photoactivated by CR and thus, enhancing its cytotoxicity. In this work, 18F-FDG was used to evaluate the effect of Cerenkov radiation on DOX, in comparison to irradiation with a 450-nm laser beam, in terms of ROS production. The production of 1O2 and O2⁎- reactive species during DOX irradiation was detected indirectly by ABMA and DCPIP bleaching, respectively. The cytotoxic effect of the DOX / 18F-FDG CR system was evaluated in the T47D breast cancer cell line. The irradiation of DOX produced 1O2 and O2⁎- species using both 18F-FDG CR and a 450-nm laser beam. The majority reactive species produced in both cases was 1O2; a favourable result, given the greater cytotoxicity of this species. The viability of T47D cells in presence of DOX (5 nM), 18F-FDG (37.5 μCi) and DOX (5 nM)/18F-FDG (37.5 μCi) was (86 ± 9)%, (84 ± 8)% and (64 ± 5)%, respectively; these results suggest a synergistic cytotoxic effect derived from the cytotoxic activity of DOX and its photoactivation by 18F-FDG CR. It is worth noting that the system could be optimized in terms of DOX concentration and 18F-FDG activity for better results. Due to the fact that 18F-FDG is widely used in nuclear imaging, the DOX/18F-FDG system also possesses theragnostic characteristics. Thus, in this work, it is demonstrated that DOX can be used in a dual therapy system based on chemotherapy-PDT when 18F-FDG CR is used as a DOX excitation source.

Conventional versus daylight photodynamic therapy for acne vulgaris: A randomized and prospective clinical study in China

Photodynamic therapy (PDT) is an effective and safe treatment modality for acne vulgaris, and a variety of light sources have been investigated. Sunlight has been used as a PDT light source in a limited number of acne studies . However, to date, a comparative study of conventional PDT (C-PDT) and daylight PDT (DL-PDT) on acne is still lacking. This study aims to assess the efficacy and safety of DL-PDT vs. C-PDT in the treatment of acne vulgaris. Eighty patients with facial moderate-to-severe acne vulgaris were randomly assigned to either DL-PDT group or C-PDT group. All patients got two to three treatment sessions at two-week intervals. The lesions were photographed with VISIA digital imaging system at baseline and weeks 2, 4, and 6. Follow-up monthly for 3 months. The endpoints include efficacy (lesion response), safety (VAS pain score) and patient satisfaction. A total of 77 patients completed the study. There was no statistical difference in objective response rate between DL-PDT group and C-PDT group at weeks 2, 4, and 6, respectively (40.0 %, 90.0 %, and 94.7 % vs. 45.0 %, 85.0 %, and 92.3 %, p > 0.05). The IGA score of DL-PDT group has no difference from C-PDT at baseline and at weeks 6, respectively (3.3 ± 0.4, 1.5 ± 0.7 vs. 3.4 ± 0.5, 1.6 ± 0.7, p > 0.05). The VAS pain score of DL-PDT group was lower than that of C-PDT group (1.8 ± 0.2, vs. 5.8 ± 0.3, p < 0.05). Adverse reactions such as mild burning sensation, erythema, dryness, crusting, scales and hyperpigmentation were all tolerated. Patient satisfaction was similar between the two groups (p > 0.05). DL-PDT is an effective and well-tolerated regimen for moderate-to-severe acne vulgaris compared with C-PDT.

Light-Emitting Diode-Based Photodynamic Therapy for Photoaging, Scars, and Dyspigmentation: A Systematic Review.

Light-emitting diodes (LEDs) may be used as an activating light source for photosensitizers in photodynamic therapy (PDT), a form of noninvasive phototherapy. Photodynamic therapy for aesthetic dermatologic conditions has demonstrated skin rejuvenating effects. To evaluate the safety and efficacy of PDT using LEDs to treat aesthetic dermatologic conditions including photoaged skin, scarring, and dyspigmentation. A search of PubMed and EMBASE databases was conducted through May 31, 2019, to identify studies that used LEDs as a light source for PDT and evaluated cosmetic improvements as the primary outcome measure. A total of 24 original articles were included in the authors' systematic review. The available evidence supports methyl aminolevulinate or 5-aminolevulinic acid incubation followed by LED treatment for global improvement of skin quality, including smoother texture, reduction of rhytides, and improvement of scars. Histologic analysis for global skin improvement demonstrated increased collagen fibers and decreased elastin fibers after LED-mediated PDT. Light-emitting diode-based PDT seems to have beneficial effects for photoaging, scars and dyspigmentation. A paucity of high-quality studies using LED-based PDT for aesthetic outcomes was found, highlighting the need for well-designed randomized control trials on this topic.

Flexible organic light-emitting diodes for antimicrobial photodynamic therapy

Bacterial infection and the growth of antibiotic resistance is a serious problem that leads to patient suffering, death and increased costs of healthcare. To address this problem, we propose using flexible organic light-emitting diodes (OLEDs) as light sources for photodynamic therapy (PDT) to kill bacteria. PDT involves the use of light and a photosensitizer to generate reactive oxygen species that kill neighbouring cells. We have developed flexible top-emitting OLEDs with the ability to tune the emission peak from 669 to 737 nm to match the photosensitizer, together with high irradiance, low driving voltage, long operational lifetime and adequate shelf-life. These features enable OLEDs to be the ideal candidate for ambulatory PDT light sources. A detailed study of OLED–PDT for killing Staphylococcus aureus was performed. The results show that our OLEDs in combination with the photosensitizer methylene blue, can kill more than 99% of bacteria. This indicates a huge potential for using OLEDs to treat bacterial infections.

Daylight photodynamic therapy with 5-aminolevulinic acid 5% gel for the treatment of mild-to-moderate inflammatory acne.

Acne vulgaris is a chronic inflammatory disease that frequently occurs in adolescence. This common condition is often treated with topical or systemic therapies according to severity. Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid is a novel drug-sparing, but time-consuming approach. Recently, sunlight exposure has been considered a quicker, safer, cheaper and more agreeable alternative light source for PDT, but efficacy has only been proven in the oncological field. This study aimed to evaluate the efficacy and tolerability of daylight PDT (DL-PDT) for the treatment of inflammatory acne vulgaris of face, chest and trunk lesions. Twenty patients with mild-to-moderate acne vulgaris were enrolled and treated with a topical gel based on 5% delta-aminolaevulinic acid, administered 4 times at 14-day intervals. Efficacy was assessed with mean lesion count, Physician Global Assessment (PGA), Investigator's Global Assessment (IGA) and patients' self-assessment (10-point scale). Compared to T0, mean inflammatory lesions count decreased in all patients at FU1, from 16.7±4.4 to 5.2±3.3 (P). No adverse events were reported, and no patients were lost to follow-up. PGA results of "excellent" or "good" improvement were reported in 95% at T3 and 90% at FU1. Patients' self-assessments was 7.6±1.0 (T3). Discomfort was 0.5±0.2 (T3 and FU1). DL-PDT seems to be an effective and tolerable therapy for the treatment of mild-to-severe inflammatory acne. This novel regimen seems to be a viable option in the panorama of acne therapies.

Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel flexible light-emitting diode unit

BackgroundPhotosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410 nm, 510 nm, 545 nm, 580 nm, and 630 nm. Although only red light around 635 nm and blue light around 400 nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred. ObjectiveWe investigated the efficacy of a flexible light-emitting diode (LED) unit that emits multiple wavelengths to improve PDT effects. MethodsHaCaT cells were incubated with 5-ALA and subsequently irradiated with either a single wavelength or sequentially with two wavelengths. Cell viability and reactive oxygen species were analyzed. Nude mice were implanted with COLO679 cells by subcutaneous injection into the flank. 5-ALA was subcutaneously injected into the tumor. The tumor was irradiated with 50 J/cm2 (day 0) and assessed daily until day 21. ResultsThe synergistic PDT effects of dual-wavelength irradiation and reactive oxygen species production were highest with the 405-nm and 505-nm wavelength combination. This dual wavelength combination was also the most effective in vivo. ConclusionWe could therefore conclude that dual-wavelength PDT is an efficient strategy for improving the therapeutic effects of PDT. Using a flexible LED unit is expected to achieve more uniform irradiation of uneven areas.

Photodynamic therapy with the use of superluminescent diodes (sLED) in the treatment of actinic keratosis.

Superluminescent diodes (sLED) appear to be an innovative and promising light source in photodynamic therapy (PDT), especially in actinic keratosis (AK) lesions treatment. Assessment of tolerability and efficacy of sLED in topical 5-aminolevulinic acid (ALA) PDT of AK lesions. 27 patients received ALA PDT with the use of sLED with "soft starter". Tolerability of sLED lamp depended on the treated lesions field (extension) rather than on their thickness. In contrast sLED lamp efficacy depended on AK lesions thickness. sLED PDT is highly effective in the treatment of grade I and II AK lesions. Grade III AK lesions require further treatment.

Low‐Dose X‐ray Activation of W(VI)‐Doped Persistent Luminescence Nanoparticles for Deep‐Tissue Photodynamic Therapy

AbstractAlthough photodynamic therapy (PDT) has served as an important strategy for treatment of various diseases, it still experiences many challenges, such as shallow penetration of light, high‐dose light irradiation, and low therapy efficiency in deep tissue. Here, a low‐dose X‐ray‐activated persistent luminescence nanoparticle (PLNP)‐mediated PDT nanoplatform for depth‐independent and repeatable cancer treatment has been reported. In order to improve therapeutic efficiency, this study first synthesizes W(VI)‐doped ZnGa2O4:Cr PLNPs with stronger persistent luminescence intensity and longer persistent luminescence time than traditional ZnGa2O4:Cr PLNPs. The proposed PLNPs can serve as a persistent excitation light source for PDT, even after X‐ray irradiation has been removed. Both in vitro and in vivo experiments demonstrate that low‐dose (0.18 Gy) X‐ray irradiation is sufficient to activate the PDT nanoplatform and causes significant inhibitory effect on tumor progression. Therefore, such PDT nanoplatform will provide a promising depth‐independent treatment mode for clinical cancer therapy in the future.