Advances in Photodynamic Therapy of Cancer

Photodynamic therapy (PDT) is based on the use of a photosensitizing agent such as porphyrins, although the earliest descriptions of PDT involved the use of eosin. Many of the molecular details of PDT are unclear, while the basic premise of PDT is simple. A photosensitizing agent, either endogenous or exogenous, is exposed to an activating light source and in the presence of oxygen produces activated intermediates, primarily singlet oxygen. Singlet oxygen is a highly reactive molecule that oxidises carbon-carbon bonds and can damage various components of the target cell (e.g., lipids, nucleic acids, etc.) directly leading to cell death. Porphyrins preferentially bind to a receptor located on the outer mitochondrial membrane called the peripheral benzodiazepine receptor. Photoactivation leads to release of mitochondrial cytochrome c and increases levels of caspases 3 and 9. Caspase 3 plays a major role in apoptosis via protein cleavage. Currently, much research is underway to help identify adjuvant treatments to potentiate the photodynamic response. Active areas of investigation include the use of agents to facilitate cutaneous penetration of photosensitizing agents, amplify the response of macrophages and other inflammatory cells, decrease angiogenesis, inhibit matrix metalloproteinase and cycloxygenase II, and activate the complement cascade. The experimental evidence is that porphyrins accumulate in the tumour tissue. Our results indicate that phenylalanine and tyrosine are the amino acids that have the most affinity in binding HpD. Recently, our investigations in vitro have sought to reduce the side effects of PDT and cytostatic therapy by using reduced amounts of compounds with a high rate of toxicity in anti-cancer protocols.