Search Results (18)

Renal cell carcinoma (RCC) presents significant therapeutic challenges due to its resistance to conventional treatments. Natural compounds with photodynamic properties, such as chlorophyll derivatives, offer potential for novel interventions. This study investigates the apoptotic effects of a chlorophyll-enriched green propolis compound activated by daylight-mediated photodynamic therapy (PDT) on RCC cells. A novel compound formulated from standardized ethanol extracts of Taiwanese green propolis, wheatgrass, and mulberry leaves was characterized using high-performance liquid chromatography (HPLC). Human RCC 786-O cells were treated with varying concentrations of the compound, with or without daylight PDT (570 nm). Cell viability was assessed via MTT assay, and median effective concentrations (EC₅₀) were calculated. HPLC analysis identified Artepillin C as the major constituent. The compound induced dose-dependent cytotoxicity, which was significantly enhanced by daylight PDT. EC₅₀ values dropped from 3.027 µL (compound alone) to 1.728 µL (with PDT), indicating synergistic efficacy. Cell viability significantly decreased in PDT-treated cells compared to non-treated controls (p < 0.05) indicating apoptosis. Daylight-activated PDT significantly amplifies the anticancer efficacy of the compound against RCC cells. Preliminary data suggest the potential of chlorophyll-enriched green propolis photodynamic activation (GPDT) as a natural adjunctive strategy for RCC, warranting further in vivo investigation. Full article

Biofilm formation on orthopedic joint implants complicates diagnosis of periprosthetic joint infections (PJIs). Sonication of explanted orthopedic implants for diagnostic enhances pathogen detection, but it shows limitations in sensitivity and handling. We investigated whether the biosurfactant saponin could improve bacterial recovery from orthopaedic implants and thereby enhance infection diagnosis ex vivo. Orthopaedic material discs of 1 cm diameter were contaminated with different clinical bacterial PJI isolates. Biofilms of Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Cutibacterium avidum, and Cutibacterium acnes were grown on the discs, which were then treated with either saline solution or various concentrations of saponin. Next, the discs were vortexed or sonicated. Colony-forming units (CFUs) enumeration and time-to-positivity of liquid cultures were determined. Additionally, a novel 3D PJI soft tissue in vitro model was established to validate these findings in a more representative scenario. Median CFU enumeration showed that 0.001% (w/v) saponin as compared to saline solution increased CFUs recovery by 2.2 log₁₀ for S. epidermidis, 0.6 log₁₀ for S. aureus, 0.6 log₁₀ for C. avidum, 1.1 log₁₀ for C. acnes, and 0.01 log₁₀ for E. coli. Furthermore, saponin treatment resulted in a >1 log₁₀ increase in S. epidermidis CFU recovery from implants in the 3D tissue model compared to standard saline sonication. With that, we propose a novel two-component kit, consisting of a saponin solution and a specialized transportation box, for the efficient collection, transportation, and processing of potentially infected implants. Our data suggest that biosurfactants can enhance bacterial recovery from artificially contaminated orthopedic implants, potentially improving the diagnosis of PJIs. Full article

Background/Objectives: Neglected tropical diseases (NTDs), such as leishmaniasis, remain a global health challenge due to limited therapeutic options and rising drug resistance. In this study, we developed an advanced nanogel formulation incorporating curcumin (CUR) and Pectis brevipedunculata essential oil (EOPb) within an F127/Carbopol 974P matrix to enhance bioavailability and therapeutic efficacy against Leishmania (Leishmania) amazonensis (LLa) promastigotes. Methods: The chemical profile of EOPb was determined through GC-MS and NMR analyses, confirming the presence of key bioactive monoterpenes such as neral, geranial, $\alpha$-pinene, and limonene. The nanogel formulation (nGPC) was optimized to ensure thermosensitivity, and stability, exhibiting a sol–gel transition at physiological temperatures. Rheological analysis revealed that nGPC exhibited Newtonian behavior at 5 °C, transitioning to shear-thinning and thixotropic characteristics at 25 and 32 °C, respectively. This behavior facilitates its application and controlled drug release, making it ideal for topical formulations. Dynamic light scattering (DLS) analysis demonstrated that nGPC maintained a stable nanoscale structure with hydrodynamic radius below 300 nm, while Fourier-transform infrared spectroscopy (FTIR) confirmed strong molecular interactions between EOPb, CUR, and the polymer matrix. Biological assays demonstrated that nGPC significantly enhanced anti-promastigote activity compared to free CUR and OEPb. Results: At the highest tested concentration (50 μg/mL EOPb and 17.5 μg/mL CUR) nGPC induced over 88% mortality in LLa promastigotes across 24, 48, and 72 h, indicating sustained efficacy. Even at lower concentrations, nGPC retained dose-dependent activity, suggesting a synergistic effect between CUR and EOPb. These findings highlight the potential of nGPC as an innovative nanocarrier for daylight photodynamic therapy (dPDT) in the treatment of leishmaniasis. Future studies will investigate the underlying mechanisms of this synergism and explore the potential application of photodynamic therapy (PDT) to further enhance therapeutic outcomes. Full article

Classical preoperative skin antisepsis is insufficient in completely eliminating bacterial skin colonization for arthroplasty. In contrast, photodynamic therapy (PDT) with red light and methyl-aminolevulinate (MAL), combined with skin antisepsis, led to the absence of bacterial growth in healthy participants, though with local skin erythema, posing an obstacle for orthopedic surgery. Therefore, we explored whether artificial daylight PDT (PDT-DL) was superior to red light. Twenty healthy participants were allocated to either 5-aminolevulinic acid-(5-ALA) PDT-DL (n = 10) or MAL-PDT-DL (n = 10) before antisepsis with povidone-iodine/alcohol. Skin swabs from the groin were taken to cultivate bacteria at baseline, after PDT-DL, and after the subsequent antisepsis. Additional swabs were taken on day 4 before and after antisepsis without PDT. The contralateral groin of each participant and of ten additional healthy volunteers served as the control (n = 30). In selected participants, 16S rRNA-based amplicon deep sequencing was performed. All participants showed a baseline bacterial colonization. After a PDT-DL with skin antisepsis, bacterial growth occurred in three (30%) and in one (10%) participants with 5-ALA and MAL, respectively, compared to the sixteen (55%) participants in the control group. On day 4, three (30%) participants per group showed positive cultures post antisepsis. Adverse effects were reported in six (60%) and zero (0%) participants for 5-ALA- and MAL-PDT-DL, respectively. The skin bacteriome changes correlated with the bacterial culture results. The MAL-PDT-DL with skin antisepsis significantly increased bacterial reduction on the skin without adverse effects. This offers an opportunity to prevent infections in arthroplasty patients and reduce antibiotic use, thus contributing to antibiotic stewardship goals emphasized in the One Health approach. Full article

Photodynamic therapy (PDT) involves the topical application of a photosensitizer and its activation by visible light, leading to the generation of protoporphyrin IX (PpIX) and reactive oxygen species. Daylight photodynamic therapy (dPDT), a variant utilizing natural sunlight as the energy source, enhances procedural flexibility by eliminating the need for specialized equipment. dPDT has been effectively used in dermatology to treat various cutaneous disorders, including neoplastic and infectious diseases. Traditionally, skin preparation and photosensitizer application are performed by trained practitioners, limiting the accessibility of dPDT for broader populations. However, recent studies suggest that these preparatory steps can be managed by patients or caregivers, enabling fully self-applied, home-based dPDT protocols. This review systematically examines the current evidence on self-applied dPDT (SA-dPDT), emphasizing molecular mechanisms and its efficacy in managing premalignant and other cutaneous conditions. Full article

This pilot study evaluated the design, usability, and practicality of the dPDT@home kit for treating actinic keratoses (AKs) on the face and scalp. The kit allowed patients to manage their treatment at home, reducing hospital visits and utilizing natural sunlight. While patients were very willing to use the kit again, further studies are required to evaluate outcomes and ascertain the need for additional improvements and support. Background/Objectives: Daylight photodynamic therapy (dPDT) is an established effective therapy for superficial mild-to-moderate actinic keratoses (AKs) on the face and scalp. In this project, we redesigned the delivery of dPDT using design principles and the concept of Realistic Medicine to create the dPDT@home kit. This user-friendly and environmentally conscious kit allows patients to manage their AKs at home, reducing the need for hospital visits and ensuring timely treatment to coincide with appropriate weather conditions and to prevent disease progression due to delays in diagnosis and treatment. The initial pilot phase of the study was to evaluate the usability and convenience of the practicalities of the dPDT@home kit. Methods: Patients were instructed to conduct two dPDT@home kit treatments approximately three weeks apart on suitable weather days. After a follow-up telephone consultation from the specialist PDT nurse following the first treatment, patients then completed an initial questionnaire (Questionnaire 1, Q1) to share their experience. A second questionnaire (Q2) was completed 3–6 months after their final treatment to assess treatment outcomes. Results: A total of 16 patients with AK on the face and/or scalp used the dPDT@home kit. Five patients formed an initial pilot group in 2020/21, whose feedback and involvement informed the final product for the larger group of eleven patients (2021/22). All patients reported no issues with receiving the kit or the pro-drug used in the treatment (Q1). Q2 had an 81.25% return rate, with an average willingness score of 8.9/10 to use dPDT@home again. However, patients expressed doubts about their confidence in the treatment’s efficacy, giving an average score of 6.9/10, with preferences leaning towards other treatments, such as hospital-based PDT or cryotherapy. Conclusions: The pilot deployment of the dPDT@home kit identified suitable patients and highlighted the need for comprehensive training and support for both patients and clinicians to deliver dPDT through this novel approach. The kit can reduce the number of hospital visits, but patients still require supervision, which can be provided remotely. The questionnaire outcomes emphasize the importance of setting patient expectations and taking a holistic approach to managing chronic field-change AK. Additionally, the kit’s recyclable components and reliance on natural sunlight promote sustainability and reduce patient travel. Further evaluation is required to determine cost-efficacy, safety, and the potential place of the dPDT@home kit in the therapeutic management of patients with this common and challenging condition. Full article

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. Full article

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. Full article

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75–5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy. Full article

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an emerging treatment option in the care of actinic keratosis (AK). A self-adhesive 5-ALA patch was recently developed that allows a precise PDT procedure. Here, we review the current literature and report the findings of our case series that observed the outcomes and safety of 5-ALA patch PDT. Ten patients with a total of 40 AKs were treated with a single session of conventional or daylight PDT using 5-ALA patch at the Department of Dermatology and Venereology, Sapienza University of Rome or at the European Institute of Oncology, Milan, Italy. Complete response was observed in three patients, while partial response was seen in seven patients. Overall tolerability was good or excellent, with local adverse events observed in four patients. This is the first case series reported where the 5-ALA patch was applied using daylight PDT, and its efficacy and tolerability in the treatment of AK were demonstrated. In conclusion, the self-adhesive 5-ALA patch is a convenient application of PDT that provides a well-tolerated and effective treatment option with satisfactory cosmetic outcomes. Full article

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is a popular treatment for actinic keratoses (AK), and several PDT treatment modalities with similar cure rates are in use. The effect relies on the activation of protoporphyrin IX (PpIX) in premalignant cells. This study aimed to measure PpIX during each treatment modality to determine the minimal PpIX activation and shortest exposure time for optimal cure rate. In four different treatment modalities, we established the PpIX formation up to three hours after MAL application without illumination and measured the speed of PpIX photoactivation during 9 min of red light (37 J/cm²). The level of PpIX three hours after MAL application was set to 100 PpIX units. In comparison, 85 PpIX units were formed during daylight PDT, 57 PpIX units during pulse PDT, and 52 PpIX units without any curettage prior to MAL. The activation of 50 PpIX units should, therefore, be enough to obtain a full effect on AK. Further, red light illumination may be shortened from 9 min to 1–2 min. The results indicate that PDT can be performed successfully with half the illumination time used in daylight PDT today and with one fourth of the illumination time used in classical PDT. Full article

Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves. Full article

Successful daylight photodynamic therapy (DPDT) relies on the interaction of light, photosensitisers and oxygen. Therefore, the ‘dose’ of light that a patient receives during treatment is a clinically relevant quantity, with a minimum dose for effective treatment recommended in the literature. However, there are many different light measurement methods used in the published literature, which may lead to confusion surrounding reliable and traceable dose measurement in DPDT, and what the most appropriate method of light measurement in DPDT might be. Furthermore, for the majority of practitioners who do not carry out any formal dosimetry and for the patients receiving DPDT, building confidence in the evidence supporting this important treatment option is of key importance. This review seeks to clarify the methodology of DPDT and discusses the literature relating to DPDT dosimetry. Full article

Graphene-based materials have garnered significant attention because of their versatile bioapplications and extraordinary properties. Graphene oxide (GO) is an extremely oxidized form of graphene accompanied by the functional groups of oxygen on its surface. GO is an outstanding platform on which to pacify silver nanoparticles (Ag NPs), which gives rise to the graphene oxide-silver nanoparticle (GO-Ag) nanocomposite. In this experimental study, the toxicity of graphene oxide-silver (GO-Ag) nanocomposites was assessed in an in vitro human breast cancer model to optimize the parameters of photodynamic therapy. GO-Ag was prepared using the hydrothermal method, and characterization was done by X-ray diffraction, field-emission scanning electron microscope (FE-SEM), transmission Electron Microscopy (TEM), energy dispersive X-rays Analysis (EDAX), atomic force microscopy and ultraviolet-visible spectroscopy. The experiments were done both with laser exposure, as well as in darkness, to examine the phototoxicity and cytotoxicity of the nanocomposites. The cytotoxicity of the GO-Ag was confirmed via a methyl-thiazole-tetrazolium (MTT) assay and intracellular reactive oxygen species production analysis. The phototoxic effect explored the dose-dependent decrease in the cell viability, as well as provoked cell death via apoptosis. An enormously significant escalation of ¹O₂ in the samples when exposed to daylight was perceived. Statistical analysis was performed on the experimental results to confirm the worth and clarity of the results, with p-values < 0.05 selected as significant. These outcomes suggest that GO-Ag nanocomposites could serve as potential candidates for targeted breast cancer therapy. Full article