Photodynamic effect

Two other aspects may be mentioned at the outset. First, fluorescent substances which accumulate preferentially in tumors (e.g., some porphyrins) may be used in diagnosis, since under appropriate irradiation (usually weak irradiation in the UV) the tumor tissue will be revealed by the fluorescence of the added substance. This is not a photodynamic effect, and is generally... 

Photodynamic therapy is based on a phenomenon known as photodynamic action, or the photodynamic effect, which are terms used to describe the damage to living tissue caused by certain photosensitizers in the presence of visible light and oxygen. Again, there is an extensive historical record, which has been reviewed several times during the 1990s.4,9-15... 

The photodynamic effect was discovered in 1900 by Raab, who showed that paramecia were not much affected by being placed in dilute solutions of acridine in the dark, but were killed when such suspensions were exposed to light.16 There was initially a considerable effort to develop these findings, but after a few years the topic seems somehow to have lost its attractiveness, and clinical reports became infrequent. 

Second, it was shown that, if the porphyrin-containing tumor so produced was irradiated with a visible (or red) light source of moderate intensity, the photodynamic effect came into operation, and photonecrosis of the tumor ensued.19 Subsequent studies, particularly by Dougherty and his colleagues,20 demonstrated the clinical promise of the technique. 

The photodynamic effect of chloroaluminum(III) phthalocyanine ((47), with C1A1 in place of Zn), a commercial product, was reported by Ben-Hur and Rosenthal.302 The photosensitizer was delivered in ethanol to cultures of Chinese hamster fibroblasts. After equilibration (16 h), exposure to visible light (fluence rate 64 Wm-2) of a suspension in PBS for 2 min gave a 3 log kill. Lack of water solubility is a problem, and for in vivo PDT of EMT-6 mammary tumors in mice a Cremophor emulsion was employed.303 The compound was a more effective PDT sensitizer than... 

The photodynamic effect on red blood cells of the /xara-tetraglucosyl-porphyrin 31a and its analogous with the sugar unit in orto position has also been analysed. Considering the possibility of the photosensitiser causing hemolysis, this study became crucial.29 The two symmetric derivatives have proved to be ineffective in these cells. However, the asymmetric derivatives 49B and 50B are phototoxic and changes in hematological parameters were observed.29... 

Yu C, Canteenwala T, Chiang LY, Wilson B, Pritzker K (2005) Photodynamic effect oh hydrophilic C60-derived nanostructures for catalytic antitumoral antibacterial applications. Synth. Metals 153 37—40. 

In two recent reports (Mroz et al., 2007b Tegos et al., 2005) we studied the photosensitizer properties of two series of three functionalized fullerene compounds, one series with polar diserinol groups (BF1-BF3), and a second series of three compounds with quaternary pyrrolidinium groups (BF4-BF6) (Fig. 4.5). The bis-substituted and tris-substituted fullerenes are actually mixtures of regioisomers of the same molecular formula due to reaction with different double bonds. We asked the question whether the photodynamic effects displayed by these compounds operated... 

Fullerenes should have a photodynamic effect on tumors, if (a) the compound is accumulated in the tumor tissue, (b) a reasonably efficient way to administer the compound to tumor bearing animals is found, and (c) enough excitation light can be delivered to the photosensitized tumors. The first report of fullerenes being used to cany out PDT of actual tumors was by Tabata in 1997 (Tabata et al., 1997). They chemically modified the water-insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a subcutaneous tumor on the back, the... 

Rosenthal I, Murali Krishna C, Riesz P, Ben-Hur E (1986) The role of molecular oxygen in the photodynamic effect of phthalocyanines. RadiatRes 107 136-142. 

Tabata Y, Murakami Y, Ikada Y (1997) Photodynamic effect of polyethylene glycol-modified fullerene on tumor. Jpn J Cancer Res 88 1108-1116. 

Yu C, Canteenwala T, Chen HH, Chen BJ, Canteenwala M, Chiang LY (1999) Hexa(sulfobutyl) fullerene-induced photodynamic effect on tumors in vivo and toxicity study in rats. Proc Electrochem Soc 99 234-249. 

In order to demonstrate that phototoxicity of C60 is in fact associated to ROS generation, we have studied photodynamic effect of fullerene in the presence of various antioxidants (AO). 

As the AO with a direct nonspecific mechanism of action we have chosen Hypoxene - sodium poly(2,5-dihydroxiphenyl)-4-thiosulfonate. Besides a direct AO effect as a scavenger of free radicals it exerts an anti-hypoxic effect shunting I and II complexes of mitochondrial respiratory chain, which are inhibited as a consequence of hypoxia (Eropkin et al., 2007). Hypoxene was introduced into cell incubation media before illumination and left during cells further incubation. Hypoxene in the concentration of 40pg/ml, comparable to doses applied in vivo, completely blocked C60-induced phototoxicity (Table 7.3). Cellular viability has completely recovered to control level, which is a convincing evidence of free radical nature of cellular damage in photodynamic effect of fullerene. 

Sharma, M., Visai, L., Bragheri, F., Christiani, I., Gupta, P. K., and Speziale, P. (2008). Toluidine Blue-mediated photodynamic effects on Staphylococcal biofilms. Antimicrob. Agents Chemother. 52, 299-305. 

Unfortunately, no more work has been done in this field. However, since amino compound degradation by singlet oxygen may play a role in biological systems, for example in photodynamic effects ( ), these reactions will probably obtain more attention in the future. 

Singlet oxygen was discovered originally by Raab who first reported the photodynamic effect of dyestuffs, light, and oxygen [311]. The biomedical implications of this discovery have only recently been made clear, particularly by Dougherty and his co-workers, who have demonstrated the implications of the photodynamic effect in tumor therapy [312]. 

McCarron, P.A., et al. 2004. Phototoxicity of 5-aminolevulinic acid in the HeLa cell line as an indicative measure of photodynamic effect after topical administration to gynaecological lesions of intraepithelial form. Pharm Res 21 1871. 

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

Figure 2 highlights the required intersection of the three elements of PDT necessary to generate 02. The principal criteria influencing each element s contribution to the photodynamic effect are also listed. 

See color plate.) Summar/ of the interaction of the three elements required for photodynamic effect. Abbreviation ... 

The importance of the unrestricted availability of molecular oxygen at the site of and throughout, the photodynamic process will be clear from earlier discussion on the formation of Cy. Namely hypoxic tissue may not provide sufficient oxygen for the photodynamic process to occur. In an environment of limited oxygen availability, longer light exposure at lower intensity may provide an effective photodynamic effect, provided that the yield of102 exceeds the tissue s ability to quench. 

---