Photodynamic treatment effects

A principal appHcation for photomedicine is the photodynamic treatment of cancer. Photochemical and clinical aspects of this topic have been reviewed (10,11). Direct irradiation of tumors coupled with adininistration of a sensitizer is used to effect necrosis of the malignancy. In this process, an excited state sensitizer interacts with dissolved in vivo to effect conversion of the oxygen from its triplet ground state to an excited singlet state, which is highly cytotoxic. In principle, excited sensitizers in either the singlet or the triplet state can effect this conversion of molecular oxygen (8). In... 

The purpose of the present study was to investigate a photodynamic inactivation of influenza vims in the allantoic fluid of chicken embryos. Further, we have evaluated nonspecific effects of photodynamic treatment on the components of biological fluids. 

Sample preparation. All allantoic fluid of chicken embryos or calf serum used in experiments contained influenza virus (104—106 EID50/ml). The samples of biological fluids underwent photodynamic treatment as described above. One milliliter aliquots were taken before treatment and at 3 and 6 h after the start of experiment. To analyze the effect of photodynamic treatment on proteins we used alkaline denaturing electrophoresis in the presence of sodium dodecylsulfate (SDS) and P-mercaptoethanol (P-ME). 

In order to compare the biological properties of the semm before and after treatment, its effect on the rate of proliferation of cells in the culture was studied. The results are presented in Table 5.1. As can be seen from these data, the proliferative activity of cells in the presence of the serum is significantly greater than that for serum-free medium. At the same time, 6 h of preliminary treatment of serum does not affect the proliferative activity of the cells. Therefore, the growth properties of the serum do not change after photodynamic treatment. 

Units and methods are developed to study the effect of active forms of oxygen on fullerene-based photosensitizers. The kinetics of the inactivation of influenza vims in saline and allantoic fluid during the course of photodynamic treatment using fullerene preparations is studied. Optimization of conditions has been conducted for viral inactivation (irradiation, doses, concentration of fullerene, and intensity of oxygen flow). Experiments are performed for inactivation of vims in blood semm. 

The bactericidal effect of photodynamic treatment (PDT) has been known for a long time (for reviews see Dai et ah, 2009 Wainwright, 1998, 2004). The method relies on illumination of microorganisms treated with nontoxic photosensitizers (PSs) by low-power visible (red, blue, or white) light. The interaction of light with PS produces highly active. 

TABLE 3.1 Killing effect of the photodynamic treatment observed for microorganisms in suspension (adapted from Brovko et at, 2009)... 

The use of photochemical treatment to stimulate translocation of endocytosed macromolecules into the cytosol is a novel technology to improve therapeutic efficacy. The technology as described in this review is derived from photodynamic therapy (PDT) and is named PCI. In both cases a photosensitizer is used in combination with light to exert the treatment effects. The basic mechanisms of the photosensitizers and their tissue interaction in combination with light will be described with emphasis on the properties of the photosensitizers used in PCI before describing the use of PCI for cytosolic delivery of macromolecules. 

Mechanisms of photodynamic effect and modes of cell death in photodynamic treatment... 

B.W. Henderson, B. Owczarczak, J. Sweeney, T. Gessner (1992). Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation. Photochem. Photobiol., 56, 513-521. 

Since 1979, photodynamic treatments of more than 200 patients suffering from chest wall recurrences have been published. The first photoradiations for controlling local and regional recurrences of breast carcinoma were performed using haemato-porphyrin derivative (HPD) [8]. Cutaneous and subcutaneous tumors were treated effectively without undue damage to overlying and adjacent skin. In 1987, dihaematoporphyrin ether (PF) was applied as photosensitizer in 18 patients with chest wall recurrences [9,10]. Complete response, reported on 105 patients photosensitized by PF, ranged between 7-91% [9-16]. 

Mitochondria have been proposed as a major subcellular target of the photodynamic effect, although other reported target organelles include plasma membranes, lysosomes and nuclei. - It was reported that photodynamic treatment can also result, directly or indirectly, in damage to DNA. However, there is evidence that such damage may not necessarily be lethal to tumor cells. ... 

Henderson, B.W. and Miller, A.C., Effects of scavengers of reactive oxygen and radical species on cell survival following photodynamic treatment in vitro comparison to ionizing radiation, Radiat. Res., 108, 196, 1986. 

Henderson, B.W., Owczarczak, B., Sweeney, J., and Gessner, T., Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation, Photochem. Photobiol, 56,513,1992. Reed, M.W., Schuschke, D.A., and Miller, F.N., Prostanoid antagonists inhibit the response of the microcirculation to early photodynamic therapy, Radiat. Res., 127, 292,1991. 

An interesting application of the photodynamic properties of porphyrins is their possible use in the treatment of certain types of cancer, a procedure called cancer phototherapy. Tumors often take up more porphyrins than do normal tissues. Thus, hematopor-phyrin or other related compounds are administered to a patient with an appropriate mmor. The mmor is then exposed to an argon laser, which excites the porphyrins, producing cytotoxic effects. 

Work during the last ten years on photodynamic therapy (PDT) has established the methodology as effective in the early treatment of cancers, and in the treattnent of certain skin disorders and viral infections. Approval by the regulatory authorities for sensitisers in this process began in 1993 when Canada allowed the use of Photofrin (QLT Therapeutics), an action followed later by most countries around the world. Now many other companies have sensitisers at late stage clinical dials (2001), see below in Table 4.5. An excellent introduction to the chemistry of this topic is provided in the book written by Bonnett. ... 

Aminolevulinic acid (ALA HCl, Levulan Kerastick) is indicated for the treatment of nonhyperkeratotic actinic keratosis of the face and scalp. It has two components, an alcohol solution vehicle and ALA HCl as a dry solid. The two are mixed prior to application to the skin. When applied to human skin, ALA is metabolized to protoporphyrin, which accumulates and on exposure to visible light produces a photodynamic reaction that generates reactive oxygen species (ROS).The ROS produce cytotoxic effects that may explain therapeutic efficacy. Local burning and stinging of treated areas of skin due to photosensitization can occur. 

Recently, it has been shown that photoactive fullerene derivatives (Cgo) were very effective in the photodynamic inactivation of bacterial viruses (bacteriophages). The treatment of water with CgQ-based PS under illumination resulted in a 2-log reduction in the number of bacteriophages in the water within only 2 min (Lee et ah, 2009). 

Several papers have been published on the photodynamic inactivation of microorganisms in waste water treatment (Acher and Juven, 1977 Gerba et al., 1977a,b, Kussovski et al., 2001 Martin and Perez-Cruet, 1987). Despite the fact that the effectiveness of photodynamic disinfection... 

Photodynamic therapy (PDT) is a developing approach to the treatment of cancer and certain other diseases, such as age-related macular degeneration, which uses a combination of a photosensitizing dye and laser light to obtain a therapeutic effect [75], There is also an absolute requirement for oxygen. If any of the... 

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