Speaker
Description
Abstract: Photodynamic therapy (PDT) has increasingly been recognised as a promising biomedical strategy for the management of diverse cancers, offering spatial and temporal selectivity compared with conventional chemotherapeutic approaches. However, its therapeutic success is critically dependent on the phototoxic potential of the photosensitiser (Ps) employed and its ability to localise within key cellular compartments and trigger downstream death pathways. In this study, we investigated the phototoxicity of Pheophorbide‑a (PPBa), a chlorophyll‑derived Ps, in Caco‑2 colorectal cancer (CRC) cells under rigorously controlled light and dark conditions to demonstrate its mechanistic effects. Cell viability was assessed using complementary assays that revealed pronounced light‑dependent cytotoxicity, whereas minimal toxicity was observed in the absence of irradiation, emphasising the selectivity of PPBa‑mediated PDT. Subcellular localisation experiments demonstrated preferential accumulation of PPBa within mitochondria, a finding of relevance given the central role of mitochondrial integrity in regulating apoptosis. This localisation correlated strongly with apoptotic signatures, including ATP depletion, nuclear condensation, and programmed cell death pathway activation. Morphological analyses further confirmed phototoxic damage, revealing characteristic features such as cell shrinkage, membrane blebbing, and chromatin condensation. Together with the functional viability data, these structural alterations highlight the potential of PPBa to induce targeted and irreversible damage upon photoactivation. Collectively, our findings provide mechanistic insights into the cellular basis of PPBa‑mediated PDT in CRC cells. By integrating functional viability assays, localisation studies, and morphological characterisation, this work demonstrates the potential of PDT as a selective and effective therapeutic modality for CRC, while also contributing to the broader understanding of Ps‑driven cancer therapy.
