HumanInsight Suppression of Resistance to Aminolevulinic Acid-based Photodynamic Therapy in Oesophageal Cell Lines by Administration of Iron Chelators in Collagen type I Matrices
Int J Radiat Biol. 2022 Aug 5:1-47. doi: 10.1080/09553002.2022.2110310. Online ahead of print.
PURPOSE Photodynamic therapy (PDT) utilizes visible light to activate cytotoxic effects of photosensitizing drugs. PDT protocols require optimization to overcome treatment resistance and to induce beneficial anti-tumor immune response. The aim of this study was to examine the possibility to suppress resistance of oesophageal cell lines to aminolevulinic acid (ALA)-PDT by administration of iron chelators to induce sufficient cell cytotoxicity under pathophysiologically relevant conditions, mimicking the advanced stages of cancer.MATERIALS AND METHODS Effects of ALA-PDT in combination with iron chelators were compared in three oesophageal cell lines in conventional monolayers and in 3D cultures based on collagen type I. Modified colony assay and fluorescence-based live cell imaging, respectively were applied. The latter was used also to test capability of pre-polarized macrophages to interact with cancer cells subjected to ALA-PDT with or without iron chelators.RESULTS Iron chelators were effective in the enhancement of ALA-PDT in all cell lines under both culture conditions. Fluorescence evaluation of cell viability in 3D cultures indicated contribution of apoptotic cell death after ALA-PDT, both with and without iron chelators. Engulfment of remnants of dead cancer cells by macrophages in 2D cultures was indicated, however, interaction between macrophages and cancer cells in 3D cultures subjected to ALA-PDT with or without iron chelators was not present.CONCLUSIONS Potential of iron chelators to enhance ALA-PDT was maintained in 3D collagen matrices. Although PDT dose (ALA concentration, light exposure time) required modification in cell line dependent manner to achieve comparable effect of PDT alone in conventional monolayers and in collagen matrices, the potential of iron chelators to suppress resistance of oesophageal cells to ALA-PDT was not influenced by fibrillar collagen matrix.
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