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).

Reactions between triplet and singlet molecules are forbidden by quantum mechanics, making oxygen relatively non-reactive at physiological conditions.

[3] Tetrapyrrolic photosensitisers in the excited singlet state (1Psen*, S>0) are relatively efficient at intersystem crossing and can consequently have a high triplet-state quantum yield.

The longer lifetime of this species is sufficient to allow the excited triplet state photosensitiser to interact with surrounding bio-molecules, including cell membrane constituents.

Nevertheless, considerable evidence suggests that the Type-II photo-oxygenation process predominates in the induction of cell damage, a consequence of the interaction between the irradiated photosensitiser and molecular oxygen.

Photosensitizers commercially available for clinical use include Allumera, Photofrin, Visudyne, Levulan, Foscan, Metvix, Hexvix, Cysview and Laserphyrin, with others in development, e.g. Antrin, Photochlor, Photosens, Photrex, Lumacan, Cevira, Visonac, BF-200 ALA,[6][7] Amphinex[8] and Azadipyrromethenes.

These molecules perform biologically important roles, including oxygen transport and photosynthesis and have applications in fields ranging from fluorescent imaging to medicine.

The fundamental porphine frame consists of four pyrrolic sub-units linked on opposing sides (α-positions, numbered 1, 4, 6, 9, 11, 14, 16 and 19) through four methine (CH) bridges (5, 10, 15 and 20), known as the meso-carbon atoms/positions.

[3] The key characteristic of a photosensitiser is the ability to preferentially accumulate in diseased tissue and induce a desired biological effect via the generation of cytotoxic species.

[16][17][18] Disadvantages associated with first generation photosensitisers include skin sensitivity and absorption at 630 nm permitted some therapeutic use, but they markedly limited application to the wider field of disease.

Haem itself is not a photosensitiser, due to the coordination of a paramagnetic ion in the centre of the macrocycle, causing significant reduction in excited state lifetimes.

The rate-limiting step in the biosynthesis pathway is controlled by a tight (negative) feedback mechanism in which the concentration of haem regulates the production of ALA.

[3] Benzoporphyrin derivative monoacid ring A (BPD-MA), marketed as Visudyne (Verteporfin, for injection), has been approved by health authorities in multiple jurisdictions, including US FDA, for the treatment of wet AMD beginning in 1999.

Purlytin has undergone Phase II clinical trials for cutaneous metastatic breast cancer and Kaposi's sarcoma in patients with AIDS (acquired immunodeficiency syndrome).

[3] Foscan has a singlet oxygen quantum yield comparable to other chlorin photosensitisers but lower drug and light doses (approximately 100 times more photoactive than Photofrin).

[3] A Lutex derivative, Antrin, has undergone Phase I clinical trials for the prevention of restenosis of vessels after cardiac angioplasty by photoinactivating foam cells that accumulate within arteriolar plaques.

[3] A liposomal formulation of zinc phthalocyanine (CGP55847) has undergone clinical trials (Phase I/II, Switzerland) against squamous cell carcinomas of the upper aerodigestive tract.

[3] A sulphonated aluminium PC derivative (Photosense) has entered clinical trials (Russia) against skin, breast and lung malignancies and cancer of the gastrointestinal tract.

Sulphonation significantly increases PC solubility in polar solvents including water, circumventing the need for alternative delivery vehicles.

[3] Silicon naphthalocyanine attached to copolymer PEG-PCL (poly(ethylene glycol)-block-poly(ε-caprolactone)) accumulates selectively in cancer cells and reaches a maximum concentration after about one day.

The compound provides real time near-infrared (NIR) fluorescence imaging with an extinction coefficient of 2.8 × 105 M−1 cm−1 and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms that may be appropriate for adriamycin-resistant tumors.

[3] Work with zinc NC with various amido substituents revealed that the best phototherapeutic response (Lewis lung carcinoma in mice) with a tetrabenzamido analogue.

Disubstituted analogues as potential photodynamic agents (a siloxane NC substituted with two methoxyethyleneglycol ligands) are an efficient photosensitiser against Lewis lung carcinoma in mice.

The ability of metallo-NC derivatives (AlNc) to generate singlet oxygen is weaker than the analogous (sulphonated) metallo-PCs (AlPC); reportedly 1.6–3 orders of magnitude less.

Comparable lifetimes for the paramagnetic species (Eu-Tex 6.98 μs, Gd-Tex 1.11, Tb-Tex < 0.2, Dy-Tex 0.44 × 10−3, Ho-Tex 0.85 × 10−3, Er-Tex 0.76 × 10−3, Tm-Tex 0.12 × 10−3 and Yb-Tex 0.46) were obtained.

[3] The +2 charged diamagnetic species appeared to exhibit a direct relationship between their fluorescence quantum yields, excited state lifetimes, rate of ISC and the atomic number of the metal ion.

[44] The method can effectively treat polymicrobial antibiotic resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus biofilms in a maxillary sinus cavity model.

[3] The first evidence that agents, photosensitive synthetic dyes, in combination with a light source and oxygen could have potential therapeutic effect was made at the turn of the 20th century in the laboratory of Hermann von Tappeiner in Munich, Germany.

Thomas Dougherty and co-workers[53] at Roswell Park Comprehensive Cancer Center in Buffalo, New York, clinically tested PDT in 1978.

It has been widely tested for its use in treating skin cancers and received FDA approval in 2000 for the treatment of wet age related macular degeneration.