Towards high-throughput light-activated drug discovery using automated plate illuminator

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.