Photodynamic Therapy Mechanisms in Cancer Treatment

Photodynamic therapy (PDT) harnesses the interplay of photosensitising agents, light of defined wavelengths and molecular oxygen to elicit a cytotoxic cascade in cancerous tissues. Upon selective accumulation of a photosensitiser within tumour cells, illumination triggers formation of reactive oxygen species (ROS), primarily singlet oxygen, which inflicts oxidative damage on subcellular organelles, including mitochondria, endoplasmic reticulum and plasma membranes. This damage provokes cell death programmes such as apoptosis and autophagy, disrupts tumour vasculature and can potentiate antitumour immunity. The intracellular localisation of the photosensitiser determines the initial site of ROS production and influences downstream signalling, including mitochondrial membrane permeabilisation, release of cytochrome c and activation of caspases, or endoplasmic reticulum stress responses. Resistance mechanisms such as elevated autophagic flux or hypoxia-induced factors may attenuate PDT efficacy. Advances in photosensitiser design, light delivery and combination strategies aim to overcome tissue penetration limits and therapeutic resistance, rendering PDT a versatile modality across a spectrum of solid tumours.

Research from Nature Portfolio

Comparative studies of prodrug and photosensitiser localisation in squamous cell carcinoma cell lines have revealed that subcellular distribution governs PDT response. In cutaneous carcinoma models, methyl-aminolevulinate localises predominantly to the plasma membrane, enhancing phototoxicity in sensitive lines, while temoporfin accumulates within lysosomes across both responsive and resistant cell types. The differential trafficking of glycogen synthase kinase 3β and the activation of nuclear transcription factors have been implicated in varied cell survival outcomes, suggesting that intracellular biomarkers may predict treatment efficacy and guide photosensitiser selection.

Photodynamic Therapy Mechanisms in Cancer Treatment publication trend

The graph below shows the total number of articles in photodynamic therapy mechanisms in cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Photodynamic Therapy: A treatment modality that employs light-activated agents to generate cytotoxic reactive oxygen species in targeted tissues.

Photosensitiser: A molecule that accumulates in tumour cells and, upon light exposure, mediates ROS production.

Reactive Oxygen Species (ROS): Highly reactive molecules derived from oxygen that induce cellular damage.

Autophagy: A regulated process by which cells degrade and recycle intracellular components, modulating survival under stress.

Apoptosis: A form of programmed cell death characterised by caspase activation and DNA fragmentation.

References

1. Cell Death Pathways in Photodynamic Therapy of Cancer. Cancers (2011).
2. Autophagy Regulation and Photodynamic Therapy: Insights to Improve Outcomes of Cancer Treatment. Frontiers in Oncology (2021).
3. Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy. PLOS ONE (2017).
4. Comparative response to PDT with methyl-aminolevulinate and temoporfin in cutaneous and oral squamous cell carcinoma cells. Scientific Reports (2024).
5. Autophagy Regulation Using Multimodal Chlorin e6-Loaded Polysilsesquioxane Nanoparticles to Improve Photodynamic Therapy. Pharmaceutics (2023).
6. Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes. International Journal of Molecular Sciences (2024).
7. Emodin combined with 5‐aminolevulinic acid photodynamic therapy inhibits condyloma acuminate angiogenesis by targeting SerRS. Journal of Cellular and Molecular Medicine (2024).