There is an ongoing need in photodynamic therapy (PDT) research to develop highly active photosensitizers (PSs) with improved characteristics combined with optimized treatment protocols to produce effective treatment with minimal side effects. While several novel PSs have undergone clinical trials or been approved in recent years, there remain few available instrumentation options for high-throughput screens (HTS) with in vitro PDT. The Modulight ML8500 was developed to address this need, facilitating HTS of potential PSs with its precisely specific control over the light component. The instrument can select from a variety of high-power, monochromatic wavelengths for screening in the context of a tumor-centered approach, whereby the light dose can be tailored to optimize for physiological conditions or limitations specific to the type of cancer. In the present case, the ML8500 was used here to characterize a series of promising ruthenium-based complexes specifically designed to target melanoma. These PSs could be activated over a broad range of wavelengths, and most importantly including in the near-infrared range, where light penetrates tissue more effectively. In a second study, osmium-based PSs were characterized with the ML8500 in normoxic and hypoxic conditions with variable light parameters (wavelength, light dose, light fluence), showing high activity even in hypoxic conditions. These are specific examples where the ML8500 successfully increased experimental flexibility, reproducibility, and throughput.
Ruthenium and osmium-based photosensitizers (PS) are compounds of interest for use in photodynamic therapy (PDT). These PS’s can be activated by light wavelengths in the range of 400-675 nm, which can be selected based on the tumor environment, treatment area, and available light sources. The objective of this study was to explore these PS’s for the treatment of several relatively aggressive cancer cell lines. A human adenocarcinoma cell line (A549) was treated with ruthenium-based compounds at concentrations of 1, 5, or 10 uM, followed by light treatment of 93 J/cm2 at either 532 nm or 630 nm. Similarly, osmium-based compounds were used to treat A549, murine melanoma (B16F10) and squamous cell carcinoma (SCCVII) cell lines at concentrations of 0.05, 1, or 3 uM, followed by light treatment of 93 J/cm2 at 630 nm. Cells survival was assessed 24 hours after PDT treatment using either alamarBlue or MTT cell viability assays. In-vitro MTT viability assays revealed that ruthenium-based compounds activated with 630 nm light showed high SCCVII cell toxicity at 5uM. AlamarBlue assays have shown that ruthenium based compounds activated by 532 nm light show high A549 cell toxicity at 1uM in-vitro. Osmium-based compounds showed optimal PDT-mediated cytotoxicity in SCCVII, A549, and B16F10 cell lines at a concentration of 1uM activated by 630 nm light, while exhibiting minimal dark toxicity. The Ruthenium and Osmium-based compounds are potentially potent PSs against lung, melanoma and squamous cell carcinoma cells, in-vitro.
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