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Background Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. Methods Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. Results Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. Conclusion Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma.

As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a significant public health burden. Among skin disorders, allergic contact dermatitis (ACD) is the most prevalent occupational disease and the most common form of immunotoxicity in humans. ACD is a T-cell-mediated skin inflammation resulting from the priming and expansion of allergen-specific CD4+ and CD8+ T cells. The clinical condition is characterized by local skin rash, itchiness, redness, swelling, and lesions, being mainly diagnosed by the patch test. Upon ACD diagnosis, avoiding the exposure to the triggering allergen is the mainstay of treatment to prevent future flares. In cases where avoidance is not possible, the use of a standard of care interim treatments such as steroid creams or ointments, barrier creams, and moisturizers are strongly recommended to alleviate symptoms. In this review, we sought to provide the reader with an overview of the pathophysiology of ACD as well as the currently available pharmacological treatment options. Furthermore, a comprehensive outline of several preventive strategies is also provided.

The discovery of Pt-chlorin-type theranostic agents is described. Luminescent Pt(II) 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, with different degrees of hydrophilicity, have been synthesized and their in vitro photocytotoxicity against human melanoma, oesophageal and bladder carcinomas was studied. A di(hydroxymethyl)-substituted chlorin was identified as a privileged molecule to explore imaging-guided photodynamic therapy. In addition to the high activity as PDT agent and absence of cytotoxicity per se, this molecule showed the ideal photophysical and photochemical properties. In vivo studies using a A375 melanoma mouse model, proved the extraordinary properties of this chlorin as a luminescent probe and the ability to impair tumor growth, making image guided treatment and follow up a possibility.

Introduction We recently developed a new type of photochemically stable platinum (II) chlorins, which are remarkable photosensitizers that can be used in photodynamic therapy (PDT), due to its therapeutic capacity. Simultaneously, due to its highly luminescence proprieties, in the biological relevant 650–850 nm red and near infrared spectral region, they may be used for biological imaging. In addition, photophysical studies indicate that they may be used as ratiometric oxygen sensors. Material and methods Compounds with different degrees of hydrophilicity were synthesised and characterised. Photocytotoxicity studies were carried out against two human tumour cell lines, the OE19 line of oesophageal carcinoma and the A375 line of melanocytic melanoma. The formulation of the sensitizers consisted in a 1 mg/mL solution in DMSO and the desired concentrations being achieved by successive dilutions. The sensitizers were administered in several concentrations (from 50 nM to 10 µM) and, 24 hour after incubation, cells were washed with PBS and new drug-free medium was added. Plates were irradiated ( Results and discussions Preliminary cytotoxicity studies indicate that, in both cell lines, platinum (II) chlorins with more hydrophilic features require lower doses of photosensitizer to induce a significant photocytotoxic effect on tumour cells. Our best results were IC50 value of 165.9 nM (confidence interval at 95%: [77.9; 356.6]) for A375 line and 498.6 nM (confidence interval at 95%: [283.5; 876.5]) for OE19 line. However, and given that the confidence intervals were too large, it was hypothesised that this type of compounds would be aggregating in the biological medium. This hypothesis was corroborated by additional photophysical studies. As such, disaggregation was performed with the use of a non-ionic surfactant since surface active agents (surfactants) has been widely used for enhancing solubilisation of poorly soluble drugs. Conclusion Although photocytotoxicity studies reveal that the platinum (II) chlorins tested would be very promising for PDT, further cytotoxicity studies will be carried out using a novel formulation. This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT): POCI-01–0145-FEDER-PTDC/QEQ-MED/0262/2014;COMPETE 2020 POCI-01–0145-FEDER-007630 and POCI-01–0145-FEDER-007440.

Introduction Photodynamic therapy (PDT) is a clinically approved therapeutic procedure, which is entering the mainstream of cancer treatments. Nowadays PDT has been successfully used in the treatment of skin cancers, but the use of PDT against melanoma can be compromised due to the natural resistance mechanism of some melanoma cancer cells. Thus, the search for new photosensitizers is a relevant research goal. Bladder cancer is also an interesting target to PDT, due to easy irradiation accessibility by cystoscopy. Material and methods A375 human melanoma cells and HT1376 human bladder cancer cells were plated. The formulation of the sensitizers consisted in a 1 mg/mL solution in DMSO and the desired concentrations being achieved by successive dilutions. The sensitizers were administered in several concentrations (from 1 nM to 10 mM) and cells were incubated for 24 hour. Controls were performed on every test. Cells were washed with PBS and new drug-free medium was added. Each plate was irradiated with a fluence rate of 7.5 mW/cm2, to reach 10 J. Evaluation by MTT assay was performed 24 hour after the photodynamic treatment in order to evaluate the cytotoxic effect. Results and discussions Our previous in vitro PDT studies demonstrated that the increase of chlorins’ hydrophilicity of leads to higher activity against A375 melanoma cells. Therefore, a series of novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins bearing dicarboxylic acid and monocarboxyic moieties were developed showing an interesting biological activity against the A375 and HT1376 cancer cells. Inhibition of the metabolic activity seems to be dependent on the concentration of the sensitizers used. With the experimental metabolic activity values, it was possible to calculate the concentration of the sensitizers that inhibits the proliferation of cultures in 50% (IC50). For this series of compounds, IC50 values ranged from mM to nM concentrations. Nevertheless, a new molecule with an IC50 value of 67,93 nM stood out. Conclusion The compounds tested were active against human melanocytic melanoma A375 cells and human bladder HT1376 cancer cells. MTT assay showed that the metabolic activity was inversely proportional to the concentration of the photosensitizer. Interestingly low IC50 values in the nanomolar range encourage further studies. Funding The Foundation for Science and Technology: POCI-01–0145-FEDER-PTDC/QEQ-MED/0262/2014; (COMPETE 2020). POCI-01–0145-FEDER-007630 and POCI-01–0145-FEDER-007440.

Introduction Considering the increased need for alternatives to current treatments, a new therapy based on plasma, the fourth state of matter, has recently raised the medical community’s attention. The aim of this work was to evaluate the effect, selectivity and mechanisms of action of cold atmospheric plasma (CAP) in a human retinoblastoma cell line. Material and methods An electronic device was designed to generate CAP, in open air above multiwell plates where Y79 cell cultures were seeded. Plasma emission spectrum was captured by a spectrometer. In order to evaluate the cytotoxicity and selectivity of CAP, metabolic activity of similarly treated Y79 and human fibroblasts HFF1 cells was measured. Apoptosis detection, analysis of mitochondrial membrane potential (MMP) and cell morphology were studied to determine the type of cell death. Propidium-iodide/RNAse staining was used to study the cell cycle and genotoxic effects were assessed by comet assay. Oxygen and nitrogen reactive species (RS) and oxidative defenses were measured. In order to explore the interaction of the electric field with voltage-gated calcium channels, blockade with verapamil was applied. Clonogenic assay screened for long term survival. Results and discussions After 60 s of CAP treatment, the metabolic activity of Y79 cells decreased more than 50%, mostly due to apoptosis, while HFF1 endured viable. Cell survival was shortened. Accumulation of Y79 cells in S and G2/M phases was recorded, nevertheless, no DNA strand breaks were detected. Plasma emission spectrum displayed several peaks in ultraviolet domain. Concerning RS, the concentration of intracellular peroxides and nitric oxide was increased. However, antioxidative defenses were not triggered and reactive oxygen species inhibitors were not capable of abrogating cytotoxic effects of CAP. Similarly, verapamil did not protect cells from death. Conclusion This study suggests a potential novel therapy based on plasma able to selectively target tumour cells while preserving the non-inflammatory environment. Funding FCT, Portugal (UID/NEU/04539/2013), FEDER-COMPETE (FCOMP-01–0124-FEDER-028417, POCI-01–0145-FEDER-007440)