LAUSR

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 (<580 nm) with a fluence rate of 7.5 mW/cm2, to reach 10 J. Controls were performed on every test. Evaluation by MTT assay was performed 24 hour after the photodynamic treatment. The IC50 values were calculated. 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 Fundação para a Ciência 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.