Thermal photodynamic therapy (PDT) is an emerging modality to optimize treatment of pre-cancerous squamous cell carcinoma (SCC) lesions, known as actinic keratoses. Thermal PDT involves heating the tissue, skin, or mucosa above normal skin temperature during 5-aminolevulinic (5-ALA) incubation and irradiating with blue light, which leads to cell apoptosis and reactive oxygen species (ROS) generation. To our knowledge, thermal PDT has not been studied for the treatment of cutaneous or mucosal SCC. We incubated two SCC cell lines with 5-ALA for 30 minutes at temperatures between 21 °C and 42 °C and then irradiated cells with 1000 seconds of blue light. We measured changes in apoptosis, necrosis, and ROS. At 36 °C, there was a dose-dependent increase in apoptosis and ROS generation. Thermal incubation of 5-ALA at 39° and 42 °C followed by blue light increased cell apoptosis and ROS generation compared to untreated control samples incubated at the same temperatures. Thermal PDT may represent a new treatment option for cutaneous and mucosal SCC cancer. Thermal PDT is associated with an increase in SCC cellular apoptosis and is associated with an upregulation in ROS. Clinical trials are required to determine optimal thermal PDT treatment parameters and efficacy for cutaneous and mucosal SCC.
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