Abstract

The development of effective cancer therapies is required to improve outcomes in colorectal cancer (CRC) treatment. Photodynamic therapy (PDT) has been proposed as more beneficial over common therapeutic approaches and is currently used to treat numerous cancer indications. PDT relies on a selective photosensitizer (PS) that gets activated by laser light in the presence of molecular oxygen, thereby inducing tumour death. To date, zinc phthalocyanine tetrasulfonate acid (ZnPcS4) - mediated photodynamic therapy (PDT) has shown strong cytotoxic effects in twodimensional (2D) cell culture. Three-dimensional (3D) structures such as multicellular cancer tumour spheroids (MCTS) are being recognised to accurately mimic similarities to the in vivo tumour tissue architecture. In this study, the cytotoxicity assessment of ZnPcS4 against MCTS established from human colorectal carcinoma (Caco-2 cell line), under irradiation at 673nm at a fluence of 10 J/cm² was evaluated. Spheroids were cultured in 96-well non adherent plates, using low attachment technique. Post treatment, MCTS morphology was characterized. Cytotoxic responses on spheroids were assessed post ZnPcS4-based PDT using lactase dehydrogenase- cytotoxicity assay and quantitative assessment of cell death mechanism using Annexin V/PI Staining protocol was conducted. ZnPcS₄ in combination with laser irradiation exerted a dose dependent increase in LDH level patterns. In addition, an induction of apoptotic cell death mechanism was observed. These findings suggest that ZnPcS₄ exhibits considerable potential as a photosensitizer for photodynamic therapy against multicellular cancer tumour spheroids.

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