Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.
Many reviews on PDT have been published. This field is now so large, and embraces so many sub-specialties, from laser technology and optical penetration through diffusing media to a number of medical fields including dermatology, gastroenterology, ophthalmology, blood sterilization and treatment of microbial-viral diseases, that it is impossible to cover all aspects in a single review. Here, we will concentrate on a few basic aspects, all important for the route of development leading PDT to its present state: early work on hematoporphyrin and hematoporphyrin derivative, second and third generation photosensitizers, 5-aminolevulinic acid and its derivatives, oxygen and singlet oxygen, PDT effects on cell organelles, mutagenic potential, the basis for tumour selectivity, cell cooperativity, photochemical internalization, light penetration into tissue and the significance of oxygen depletion, photobleaching of photosensitizers, optimal light sources, effects on the immune system, and, finally, future trends.
Most of the positive effects of solar radiation are mediated via ultraviolet-B (UVB) induced production of vitamin D in skin. However, several other pathways may exist for the action of ultraviolet (UV) radiation on humans as focused on in this review. One is induction of cosmetic tanning (immediate pigment darkening, persistent pigment darkening and delayed tanning). UVB-induced, delayed tanning (increases melanin in skin after several days), acts as a sunscreen. Several human skin diseases, like psoriasis, vitiligo, atopic dermatitis and localized scleroderma, can be treated with solar radiation (heliotherapy) or artificial UV radiation (phototherapy). UV exposure can suppress the clinical symptoms of multiple sclerosis independently of vitamin D synthesis. Furthermore, UV generates nitric oxide (NO), which may reduce blood pressure and generally improve cardiovascular health. UVA-induced NO may also have antimicrobial effects and furthermore, act as a neurotransmitter. Finally, UV exposure may improve mood through the release of endorphins.
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