Photosensitization
by Dr. Susana Encinas
Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, Spain.
Photosensitization is the process by which a photochemical or photophysical alteration occurs in one molecular entity as a result of initial absorption of radiation by another molecular entity called aphotosensitizer. In mechanistic photochemistry the term is limited to cases in which the photosensitizer is not consumed in the reaction.[1]
The photosensitization phenomenon can be applied to many fields such as that of photocatalysis where light is used to activate a substance, the photocatalyst, which modifies the rate of a chemical reaction without being involved itself in the chemical transformation.Within the numerous areas in which the concept of photosensitization can be applied, the contents here will be related to the biological subject. Thus, photosensitization is the process whereby a molecule activated by light is able to induce photoreactions in the biomolecules present in its environment (see Figure 1). The process is generally associated with the absorption of normal and harmless doses of light by a "strange" molecule (photosensitizer, PS) in non-harmful concentrations, reaching the absorbed energy to the constituents of tissues and cells. In the absence of this substance, the system is not affected by light provided that direct light absorption is not possible. In humans, the eyes and skin are the main receptors of light. In most cases, photosensitized reactions in the skin give rise to adverse side effects. In fact, the photosensitizing deoxyribonucleic acid (DNA) damage by xenobiotics has attracted considerable attention because it can involve a more extended active fraction of the solar spectrum with carcinogenic potential. In that way, the risk of biomolecules damage is considerably increased. However, photosensitization can also be used for therapeutic purposes, what is called photodynamic therapy (PDT).[2]
Photosensitizers are photochemically activated, and there is no direct absorption of light by biomolecules. The light that activates most photosensitizers falls under the UVA range, although there are also some substances whose spectrum of action extends to UVB (see Photoprotection entry for ultraviolet (UV) regions). On the other hand, UVA radiation penetrates deeper into the skin and reaches these molecules, which are distributed in the deeper levels of cutaneous tissue. The main source of UVA radiation is the sun, but it is also emitted by artificial light sources, such as tanning lamps and fluorescent lights, the latter to a lesser degree.[3,4]
Sun-induced skin reactions have been increasing in recent decades, due not only to social causes such as tanning, but also to the high number of photosensitizing products commonly used by contact or ingestion, which are found in plants, pharmaceuticals, food additives, chemical fertilizers, dyes, sunscreens, cosmetics, etc. This phenomenon attracts, more and more, the interest of dermatologists, the pharmaceutical industry and legislative bodies involved in the topic. Changing living habits in developed countries leads to a frequent combination of light and chemicals.
Cutaneous photosensitizers may be (a) exogenous, foreign chemicals introduced into the skin by topical or parenteral route, or (b) endogenous, biomolecules (DNA and melanin, for example) in high concentrations or metabolites. Drugs are the major exogenous source of photosensitizing reactions in the skin.[5]
Photosensitivity Side Effects
As previously mentioned, the combined action of drugs and sunlight on patients can produce both desired and undesired effects. Thus, PUVA-therapy (psoralens plus UVA-radiation) has long been employed for the treatment of psoriasis, while porphyrins are currently being introduced for the photodynamic therapy of cancer or other diseases. By contrast, there are also a significant number of reports indicating that a variety of drugs can elicit undesired side effects, such as phototoxicity, photoallergy, or photocarcinogenicity.[2,4] Photosensitivity is a broad term used to describe an adverse reaction to light, which may be phototoxic or photoallergic in nature.
In order to anticipate the appearance of photosensitivity side effects, a mechanistic understanding of the involved phenomena is necessary (Figure 2). Absorption of sunlight by drugs leads to their excited states. These can proceed further to afford drug-derived reactive intermediates or, under aerobic conditions, reactive oxygen species. Any of the above short-lived chemical entities may be able to interact with biological substrates (targets), ultimately producing photodamage. Then, extensive changes of biomolecules upon irradiation in the presence of drugs are thought to be responsible for the occurrence of photosensitization side effects.[3] Figure 2. [math]PS\xrightarrow[]{h\nu (UVA)}PS^{*}\xrightarrow[]{Target(A)}PS+A^{*}\rightarrow Photoproducts[/math]
