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Photodynamic therapy (PDT) is a technique with well-established principles that often demands repeated applications for sequential elimination of tumor cells. An important question concerns the way surviving cells from a treatment behave in the subsequent one. Threshold dose is a core concept in PDT dosimetry, as the minimum amount of energy to be delivered for cell destruction via PDT. Concepts of threshold distribution have shown to be an important tool for PDT results analysis in vitro. In this study, we used some of these concepts for demonstrating subsequent treatments with partial elimination of cells modify the distribution, which represents an increased resistance of the cells to the photodynamic action. HepG2 and HepaRG were used as models of tumor and normal liver cells and a protocol to induce resistance, consisted of repeated PDT sessions using Photogem® as a photosensitizer, was applied to the tumor ones. The response of these cells to PDT was assessed using a standard viability assay and the dose response curves were used for deriving the threshold distributions. The changes in the distribution revealed that the resistance protocol effectively eliminated the most sensitive cells. Nevertheless, HepaRG cell line was the most resistant one among the cells analyzed, which indicates a specificity in clinical applications that enables the use of high doses and drug concentrations with minimal damage to the surrounding normal tissue.

A combination of metabolic modifications by light stimulus and photodynamic action is very attractive. Photobiomodulation therapy (PBMT) comprehends a vast range of applications and has been shown to be suitable to ease morbidities caused by chemotherapy and radiation, such as mucositis and dermatitis. The current study investigates the effects of near-infrared PBMT combined with porphyrin-based photodynamic therapy (PDT) in squamous cell carcinoma cell lines SCC-25 and SCC-4. The aim is to evaluate the potential of this combination to improve PDT outcome by increasing cell toxicity. Many techniques were used to verify the combined effect. Photobiomodulation (PBM) enhanced PDT action in SCC-25 cells by increasing photosensitizer (PS) uptake and production of reactive oxygen species (ROS). The equivalent was not seen in SCC-4 cells compared to the PDT only group. We believe these effects are strongly related to the interval of application between PBMT, PS incubation and PDT. Additionally, the effect of ascorbic acid on preventing PBM effects in PDT shows that ROS play an important role in the early mechanisms of PBM-PDT. Therefore, we believe PBM-PDT combination is worth exploring, for its benefit-cost ratio and simple protocols, along with the possibility of improvement in treatment resuts.