Search Results (10)

5-Aminolevulinic acid (5-ALA) is used clinically for photodynamic therapy and fluorescence-guided diagnosis and surgery due to its selective accumulation in malignant cells, where it is converted into photoactive protoporphyrin IX (PpIX) via the heme biosynthesis pathway. The resulting buildup allows for selective visualization or destruction of the tissue under specific light exposure, particularly in pre-malignant and malignant skin lesions, brain tumors, and bladder cancer. More recently, 5-ALA and 5-ALA-induced PpIX have attracted interest for emerging diagnostic and therapeutic approaches. For instance, PpIX is being investigated as a potential marker for liquid biopsy. PpIX-mediated photodynamic therapy also shows promise for targeting specific cancer cell populations, including dormant cancer cells and cancer stem cells. In addition, the benefits of 5-ALA in neurological and mental health are under investigation, as disruptions in heme biosynthesis are increasingly linked to neurodegenerative diseases, chronic fatigue, and mood and sleep disorders. This review highlights these expanding research directions, discusses current challenges, and explores potential opportunities for 5-ALA-based applications. Full article

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

Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials. Full article

The persistent failure of standard chemotherapy underscores the urgent need for innovative and targeted approaches in cancer treatment. Photodynamic therapy (PDT) has emerged as a promising photochemistry-based approach to address chemoresistance in cancer regimens. PDT not only induces cell death but also primes surviving cells, enhancing their susceptibility to subsequent therapies. This review explores the principles of PDT and discusses the concept of photodynamic priming (PDP), which augments the effectiveness of treatments like chemotherapy. Furthermore, the integration of nanotechnology for precise drug delivery at the right time and location and PDT optimization are examined. Ultimately, this study highlights the potential and limitations of PDT and PDP in cancer treatment paradigms, offering insights into future clinical applications. Full article

The introduction of strong-field ligands can enable luminescence in first-row transition-metal complexes. In this way, earth-abundant near-infrared emitters can be obtained using early 3d metals. A prime example is the molecular ruby [Cr(ddpd)₂]³⁺ (ddpd = N,N′-dimethyl-N,N′-dipyridin-2-ylpyridine-2,6-diamine) that can achieve high phosphorescence quantum yields at room temperature in aqueous solution. To understand these remarkable properties, here, we simulate its photodynamics in water using trajectory surface hopping on linear vibronic coupling potentials parametrized from multiconfigurational CASSCF/CASPT2 calculations. We find that after excitation to the second absorption band, a relaxation cascade through metal-centered states occurs. After an initial back-and-forth intersystem crossing with higher-lying doublet states, the complex relaxes through a manifold of quartet metal-centered states to the low-lying doublet metal-centered states which are responsible for the experimentally observed emission. These electronic processes are driven by an elongation of the Cr–ligand bond lengths as well as the twisting motion of the trans-coordinated pyridine units in the ddpd ligands. The low-lying doublet states are reached within 1–2 ps and are close in geometry to the doublet minima, thus explaining the high phosphorescence quantum yield of the molecular ruby [Cr(ddpd)₂]³⁺. Full article

Photodynamic therapy (PDT), which combines light and oxygen with a photosensitizer to induce reactive oxygen species (ROS)-mediated killing of primary tumor cells, benefits from non-invasive properties and its negligible toxicity to surrounding healthy tissues. In this study, we have shown that the second-generation photosensitizer FOSCAN can be internalized by tumor cells and effectively induce tumor cell death when exposed to laser irradiation in vitro. In addition, these dying tumor cells can be phagocytosed by dendritic cells and lead to their activation and maturation as assessed by in vitro co-culture models. While PDT induces immunogenic tumor cell apoptosis, its application for the treatment of tumors located in deep tissues and advanced malignancies has been limited. In this study, we demonstrate that hepatitis B core virus-like particles (HBc VLPs) can serve as a vaccine to enhance PDT-induced anti-cancer immunity by priming humoral immune responses and inducing CD8⁺ T cell responses. The combination of PDT and HBc VLPs increased the survival rate of MC-38 tumor-bearing mice to 55%, compared to 33% in PDT alone and no tumor-free mice in vaccine alone. Moreover, the combination effectively prevented tumor recurrence in vivo through enhanced immune memory T cells after therapy. Therefore, as both are clinically approved techniques, this combination provides a promising strategy for cancer therapy. Full article

Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates. Full article

The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E₂ receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists. Full article

The potential of dendritic cell (DC)-based immunotherapy to treat cancer is, nowadays, well documented. Still, the clinical success of immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening tumors that are regarded as nonimmunogenic, such as mesothelioma, however, T helper 1 immunity-biased DC-based immunotherapy could still represent an attractive strategy. In this study, we took advantage of photodynamic therapy (PDT) to induce immunogenic cell death to generate mesothelioma cell lysates for DC priming and evaluated such a vaccine to treat peritoneal mesothelioma. We found that the white light in vitro activation of the photosensitizer OR141 led to mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a PDT-based DC vaccine to mice bearing peritoneal mesothelioma led to highly significant survival when compared with sham or control animals treated with anti-CTLA4 antibodies. This was further supported by a strong CD8⁺ and CD4⁺ T cell response, characterized by an increased proliferation, cytotoxic activities and the expression of activation markers, including interferon gamma (IFNγ). Moreover, the PDT-based DC vaccine led to a significant increase in IFNγ⁺ T cells infiltered within mesothelioma, as determined by flow cytometry and immunohistochemistry. Finally, in vivo tracking of intraperitoneally administered DCs led us to document rapid chemotaxis towards tumor-occupied lymphatics (vs. lipopolysaccharide (LPS)-treated DC). DCs pulsed with PDT-killed mesothelioma cells also exhibited a significant increase in CCR7 receptors, together with an intrinsic capacity to migrate towards the lymph nodes. Altogether, these results indicate that PDT-based DC vaccination is particularly suited to induce a potent immune response against peritoneal mesothelioma. Full article

Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators. Activation of the innate immune response is necessary for subsequent induction of the adaptive arm of the immune system. This includes the priming of tumor-specific cytotoxic T lymphocytes (CTL) that have the capability to directly recognize and kill cells which display an altered self. The past decades have brought increasing appreciation for the importance of the generation of an adaptive immune response for long-term tumor control and induction of immune memory to combat recurrent disease. This has led to considerable effort to elucidate the immune effects PDT treatment elicits. In this review we deal with the progress which has been made during the past 20 years in uncovering the role of PDT in the induction of the tumor-specific immune response, with special emphasis on adaptive immunity. Full article