Photodynamic therapy

Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death (phototoxicity).

PDT is used in treating acne, wet age-related macular degeneration, psoriasis, and herpes. It is used to treat malignant cancers, including head and neck, lung, bladder and skin.

Advantages lessen the need for delicate surgery and lengthy recuperation and minimal formation of scar tissue and disfigurement. A side effect is the associated photosensitisation of skin tissue.

PDT applications involve three components: a photosensitizer, a light source and tissue oxygen. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce radicals and/or reactive oxygen species. These are free radicals (Type I) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II).

PDT is a multi-stage process. First a photosensitiser, ideally with negligible toxicity other than its phototoxicity, is administered in the absence of light, either systemically or topically. When a sufficient amount of photosensitiser appears in diseased tissue, the photosensitiser is activated by exposure to light for a specified period. The light dose supplies sufficient energy to stimulate the photosensitiser, but not enough to damage neighbouring healthy tissue. The reactive oxygen kills the target cells.

In air and tissue, molecular oxygen (O₂) occurs in a triplet state, whereas almost all other molecules are in a singlet state. Reactions between triplet and singlet molecules are forbidden by quantum mechanics, making oxygen relatively non-reactive at physiological conditions. A photosensitizer is a chemical compound that can be promoted to an excited state upon absorption of light and undergo intersystem crossing (ISC) with oxygen to produce singlet oxygen. This species is highly cytotoxic, rapidly attacking any organic compounds it encounters. It is rapidly eliminated from cells, in an average of 3 μs.

When a photosensitiser is in its excited state (3Psen*) it can interact with molecular triplet oxygen (³O₂) and produce radicals and reactive oxygen species (ROS), crucial to the Type II mechanism. These species include singlet oxygen (¹O₂), hydroxyl radicals (•OH) and superoxide (O₂⁻) ions. They can interact with cellular components including unsaturated lipids, amino acid residues and nucleic acids. If sufficient oxidative damage ensues, this will result in target-cell death (only within the illuminated area).

When a chromophore molecule, such as a cyclic tetrapyrrolic molecule, absorbs a photon, one of its electrons is promoted into a higher-energy orbital, elevating the chromophore from the ground state (S0) into a short-lived, electronically excited state (Sn) composed of vibrational sub-levels (Sn′). The excited chromophore can lose energy by rapidly decaying through these sub-levels via internal conversion (IC) to populate the first excited singlet state (S1), before quickly relaxing back to the ground state.