Search Results (152)

Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. Materials and Methods: A pre-defined protocol was registered in PROSPERO (CRD42021225182). Systematic searches in Medline, Embase, and Central, along with manual trial register searches, identified studies reporting participant clearance rates (PCR) or recurrence rates (PRR). Quality assessment for randomized controlled trials (RCTs) was conducted using the Cochrane Risk of Bias tool 2. Uncontrolled studies were evaluated using the tool developed by the National Heart, Lung, and Blood Institute. The generalized linear mixed model was used to pool proportions for uncontrolled studies. A pairwise meta-analysis for RCTs was applied, using the odds ratio (OR) as the effect estimate and the GRADE approach to evaluate the quality of the evidence. Adverse events were analyzed qualitatively. Results: A comprehensive inclusion of 36 studies facilitated an evaluation of 614 participants for PCR, and 430 patients for PRR. Diclofenac showed the lowest PCR (0.53, 95% confidence interval (CI) [0.41; 0.66]), while CO₂ laser showed the highest PCR (0.97, 95% CI [0.90; 0.99]). For PRR, Er:YAG laser showed the highest rates (0.14, 95% CI [0.08; 0.21]), and imiquimod the lowest (0.00, 95% CI [0.00; 0.06]). In a pairwise meta-analysis, the OR indicated a lower recurrence rate for Er:YAG ablative fractional laser (AFL)-primed methyl-aminolevulinate photodynamic therapy (MAL-PDT) (Er:YAG AFL-PDT) compared to methyl-aminolevulinate photodynamic therapy (MAL-PDT) alone (OR = 0.22, 95% CI [0.06; 0.82]). The CO₂ laser showed fewer local side effects than the Er:YAG laser, while PDTs caused more skin reactions. Due to qualitative data, comparability was limited, highlighting the need for individualized treatment. Conclusions: This study provides a complete and up-to-date evidence synthesis of practice-relevant interventions for AC, identifying the CO₂ laser as the most effective treatment and regarding PCR and imiquimod as most effective concerning PRR. Full article

1,3-Diphenylisobenzofuran (DPBF) is a widely used fluorescent probe for singlet oxygen (¹O₂) detection in photodynamic applications. In this work, we present an integrated experimental and computational analysis to describe its spectroscopic, photophysical, and reactive properties in ethanol, DMSO, and DMF. UV-Vis and fluorescence measurements across a wide concentration range show well-resolved S₀ → S₁ electronic transition of a π → π* nature with small red shifts in polar aprotic solvents. Fluorescence lifetimes increase slightly with solvent polarity, showing stabilization of the excited state. The 2D PES and Boltzmann populations analysis indicate two co-existing conformers (C_s and C₂), with C_s being slightly more stable at room temperature. TD-DFT calculations have been performed using several density functionals and the 6-311+G(2d,p) basis set to calculate absorption/emission wavelengths, oscillator strengths, transition dipole moments, and radiative lifetimes. Overall, cam-B3LYP and ωB97X-D provided the best agreement with experiments for the photophysical data across all solvents. The photophysical behavior of DPBF upon interaction with ¹O₂ can be explained by a small-barrier, two-step reaction pathway that goes through a zwitterionic intermediate, resulting in the formation of 2,5-endoperoxide. This work explains the photophysical properties and reactivity of DPBF, therefore providing a solid basis for future studies involving singlet oxygen. Full article

In this study, a pH-responsive nanophotosensitizer (MT@Ce6) was rationally developed by strategic integration of MIL-101 (Fe)-NH₂ metal–organic framework with tannic acid (TA) and chlorin e6. This nanocomposite exhibits pH-responsive degradation in acidic microenvironments, facilitating Fe³⁺ release and subsequent reduction to Fe²⁺ that catalyzes Fenton reaction-mediated hydroxyl radical (•OH) generation. This cascade reaction shifts reactive oxygen species (ROS) predominance from transient singlet oxygen (¹O₂) to the long-range penetrative •OH, achieving robust biofilm disruption and over 90% eradication of methicillin-resistant Staphylococcus aureus (MRSA) under 660 nm irradiation. In vivo evaluations revealed accelerated wound healing with 95% wound closure within 7 days, while species-selective antibacterial studies demonstrated a 2.3-fold enhanced potency against Gram-positive bacteria due to their unique peptidoglycan-rich cell wall architecture. These findings collectively establish a microenvironment-adaptive nanoplatform for precision antimicrobial interventions, providing a translational strategy to address drug-resistant infections. Full article

Due to rising antibiotic resistance, it is necessary to develop alternative ways to combat pathogenic bacteria. One alternative is photodynamic antibacterial chemotherapy (PACT). This work presents the conjugation of the photosensitizer Rose Bengal (RB) to lectins to improve its efficacy against Gram-positive and Gram-negative bacteria. Two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), were covalently linked to RB. Spectroscopic and chromatographic data confirmed successful conjugation. Microscopic examination demonstrated that both lectins agglutinate cells of Gram-positive S. aureus, including clinical multidrug-resistant MRSA strains, and Gram-negative E. coli, P. aeruginosa, and S. paratyphi B, although ConA showed a more pronounced reaction. Photodynamic assays showed that ConA-RB achieved complete eradication of S. aureus at significantly lower concentrations and light doses than free RB or WGA-RB. ConA-RB also exhibited higher efficacy against Gram-negative bacteria compared to free RB at lower concentrations and shorter illumination periods. WGA-RB was less effective, showing preferential activity against S. aureus. Our findings suggest that lectin–RB conjugates offer a promising approach for selective antibacterial treatment under illumination. Full article

Lipid peroxidation (LPO) is a biochemical process through which lipids are subjected to a peroxidation reaction in the presence of free radicals. The process can cause alterations in biological membranes and the formation of substances harmful to the body that can form aggregates with proteins and nucleic acids. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) are the main products of LPO. These compounds have cytotoxic and genotoxic properties and contribute to the pathogenesis of various diseases. This research focuses on the correlation between LPO and skin diseases. For some skin diseases, such as psoriasis, vitiligo, and alopecia, LPO products have been shown to have a clear role in the pathogenesis of the disease. Lipid aldehydic products like MDA and 4-HNE can enhance inflammation by stimulating pro-inflammatory genes and producing cytokines. Furthermore, these products can stimulate cell death and increase oxidative stress. For other diseases (atopic dermatitis, urticaria, pemphigus, and melanoma), the role of LPO is unclear, even if the levels of LPO biomarkers are elevated in proportion to the severity of the disease. LPO can also be exploited to counteract the proliferation of neoplastic cells. Therefore, enhancing LPO would play an adjuvant role in the therapy of neoplastic diseases such as melanoma. In particular, the therapeutic implication resulting from the role of LPO products in the cytotoxicity induced by photodynamic therapy used for the adjuvant treatment of melanoma could be of interest in the future. Full article

In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV–visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed. Full article

Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers. Full article

As a non-invasive modality, sonodynamic therapy (SDT) offers several advantages in cancer treatment, including deep tissue penetration and precise spatiotemporal control, resulting from the interplay between low-intensity ultrasound and sonosensitizers. Piezoelectric materials, known for their remarkable capacity of interconversion of mechanical and electrical energy, have garnered considerable attention in biomedical applications, which can serve as pivotal sonosensitizers in SDT. These materials can generate internal electric fields via ultrasound-induced mechanical deformation, which modulates the alteration of charge carriers, thereby initiating surface redox reactions to generate reactive oxygen species (ROS) and realizing the therapeutic efficacy of SDT. This review provides an in-depth exploration of piezoelectric materials utilized in SDT, with a particular emphasis on recent innovations, elucidation of underlying mechanisms, and optimization strategies for advanced biomedical piezoelectric materials. Furthermore, the incorporation of piezoelectric sonosensitizers with immunotherapy, photodynamic, chemodynamic, and chemotherapy is explored, emphasizing their potential to enhance cancer therapy outcomes. By examining the basic principles of the piezoelectric effect and its contributions to SDT, this review sheds light on the promising applications of piezoelectric materials in oncology. It also highlights future directions for improving these materials and expanding their clinical utility in tumor sonodynamic therapy. Full article

Background: Onychomycosis is the most prevalent nail disease, posing a challenge for health professionals in terms of treatment. Conventional topical antifungal treatments can often prove insufficient, and the use of oral antifungal drugs carries a high frequency of adverse events and drug–drug interactions. Objective: The primary aim of this study was to determine the cure rate of onychomycosis using a combined treatment of diode laser and photodynamic therapy with red-laser photodynamic therapy (PDT) and toluidine blue gel. Methods: A series of onychomycosis cases were treated and monitored for 6 months with eight applications of diode laser therapy. This treatment was combined with three applications of red-laser PDT paired with toluidine blue gel. Clinical cure was evaluated one week after the treatment’s conclusion, while mycological cure was assessed via microbiological culture. Results: The study included 12 patients and a total of 17 nails. At the end of treatment, clinical, mycological, and complete cure rates were 100% for all patients and nails. No adverse reactions were reported during or after the PDT application. However, all patients experienced pain during laser application, and two patients experienced hematoma and subungual blistering post-treatment. Two patients (2/12) experienced recurrence in three nails (3/17; recurrence rate: 17.6%) within 6 months following treatment. Conclusions: The combination of diode laser therapy and red-laser PDT with toluidine blue gel seems effective and safe for the treatment of mild, moderate, and severe onychomycosis. Full article

Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for PDT, ERI has a high hydrophilic profile that impacts its activity. To solve this, the combination of ERI with thermoresponsive and bioadhesive polymers may prove effective. Bio/mucoadhesive and thermoresponsive systems have attracted increasing interest in the development of novel pharmaceutical formulations for topical applications due to their ability to improve adhesion to the mucosa and prolong the residence time at the application site. In this study, systems based on poloxamer 407 (P407) in combination with cellulose derivatives (HPMC and NaCMC) were optimized, aiming at the topical release of ERI for PDT. The results demonstrated that the formulations containing low concentrations of cellulose derivatives exhibited greater adhesiveness and consistency at physiological temperature (37 °C), favoring the maintenance of the system at the application site. Regarding the gelation temperature (T_sol/gel), the formulations displayed values close to body temperature. The formulations with NaCMC showed a slightly higher T_sol/gel compared to HPMC ones, but it was adjustable by the polymer concentration. The addition of ERI influenced the mechanical and adhesive properties of the systems. In formulations containing HPMC, high concentrations of ERI increased bio/mucoadhesiveness, while in systems with NaCMC, the presence of ERI reduced this property. In both cases, the formulations maintained high consistency at 37 °C, contributing to the control of the active release at the application site. Rheological analysis revealed non-Newtonian behavior in all formulations, with greater consistency and elasticity at high temperatures. P407 was mainly responsible for the thermoresponsive transition from sol to gel, conferring desirable characteristics for topical application. Photodynamic activity was relevant in both formulations containing NaCMC and HPMC, which demonstrated greater capacity for degrading uric acid under light exposure. These systems are promising for the controlled release of drugs in photodynamic therapy, providing prolonged retention in the target tissue and maximizing the therapeutic efficacy of ERI. Full article

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance. Full article

The application of light-responsive nanomaterials (LRNs) in bone tissue engineering shows broad prospects, especially in promoting bone healing and regeneration. With a deeper understanding of the mechanisms of bone defects and healing disorders, LRNs are receiving increasing attention due to their non-invasive, controllable, and efficient properties. These materials can regulate cellular biological reactions and promote bone cell adhesion, proliferation, and differentiation by absorbing specific wavelengths of light and converting them into physical and chemical signals. In addition, the unique surface morphology and biocompatibility of LRNs enable them to effectively load drugs in bone tissue engineering, achieve precise release, and optimize the bone regeneration process. Through photothermal and photodynamic therapy, these materials also possess antibacterial properties and can play an important role in the repair of infectious bone defects. Although LRNs have shown significant advantages in bone tissue regeneration, a series of challenges still need to be overcome to achieve their widespread and effective clinical applications. This article summarizes the basic principles, classification, and potential applications of LRNs in bone tissue regeneration, aiming to provide reference for future research and clinical applications. Full article

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology. Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the aortic valve by aiming a laser at the aortic valve for 60 min after the administration of a photosensitizer 24 h prior. ROS, laser, and sham groups (n = 7 each) for every observation period (t = 0; t = 8 d; t = 84 d; t = 168 d) were established. The amount of ROS generation; morphological changes; inflammatory, immune, and apoptotic reactions; and hemodynamic changes in the aortic valves were assessed using appropriate histological, immunohistological, immunohistochemical, and echocardiographic methods. Results: The ROS group displayed an increased amount of ROS (p < 0.01) and increased inflammatory activation of the endothelium (p < 0.05) at t = 0. In the ROS group, aortic valves were calcified (p < 0.05) and the transvalvular gradient was increased (p < 0.01) at t = 168 d. Conclusion: The small animal model employed here may serve as a platform for analyzing ROS’s isolated role in the DAVD context. Full article

Photocatalysis has attracted more and more attention as a possible solution to environmental, water, and energy crises. Although some photocatalytic materials have already proven to perform well, there are still some problems that should be solved for the broad commercialization of photocatalysis-based technologies. Among them, cheap and easy recycling, as well as stability issues, should be addressed. Accordingly, the application of gels, either as a photocatalytic material or as its support, might be a good solution. In this review, various propositions of gel-based photocatalysts have been presented and discussed. Moreover, an easy nanoarchitecture design of gel-based structures enables fundamental studies, e.g., on mechanism clarifications. It might be concluded that gels with their unique properties, i.e., low density, high specific surface area, great porosity, and low-cost preparation, are highly prospective for solar-energy-based reactions, water treatment, photodynamic cancer therapies, and fundamental research. Full article

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (¹O₂) through Type II photochemical reactions, along with superoxide anion radicals (O₂^•−), hydrogen peroxide (H₂O₂), and hydroxyl radicals (^•OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation. Reactive oxygen species explicit dosimetry (ROSED) quantifies the reacted oxygen species concentration ([ROS]_rx) by explicit measurements of light fluence (rate), photosensitizer concentration, and tissue oxygen concentration. Here we determine tissue oxygenation from non-invasive diffuse correlation spectroscopy (DCS) measurement of tumor blood flow using a conversion factor established preclinically. In this study, we have enrolled 24 pleural PDT patients into the study. Of these patients, we are able to obtain data on 20. Explicit dosimetry of light fluence, Photofrin concentration, and tissue oxygenation concentrations were integrated into the ROSED model to calculate [ROS]_rx across multiple sites inside the pleural cavity and among different patients. Large inter- and intra-patient heterogeneities in [ROS]_rx were observed, despite identical 60 J/cm² light doses, with mean [ROS]_rx,meas of 0.56 ± 0.26 mM for 13 patients with 21 sites, and [ROS]_rx,calc1 of 0.48 ± 0.23 mM for 20 patients with 76 sites. This study presented the first comprehensive analysis of clinical ROSED in pleural mesothelioma patients, providing valuable data on future ROSED based pleural PDT that can potentially produce uniform ROS and thus improve the PDT efficacy for Photofrin-mediated pleural PDT. Full article