Sensitizer photodynamic therapy

A.M. Fisher, A. Ferrario, N. Rucker, S. Zhang, C.J. Gomer (1999). Photodynamic therapy sensitivity is not altered in human tumor cells after abrogation of p53 function. Cancer Res., 59, 331-335. 

Given stringent requirements for effective sensitizers and the desire to use wavelengths further to the red for therapeutic appHcations, definition of newer sensitizers has been a principal area of research since about 1987. Expanded theoretical and experimental understanding of photophysics has been a key element in identifying new classes of potential sensitizers (93—98). Research has focused on cationic derivatives of Nile Blue (93), metaHo-phthalocyanines (94), naphthalocyanines (95), chlorin-type compounds (96), expanded ring porphyrinoids (97), as well as porphyrins other than hematoporphyrin and its derivatives (98). This work has also been reviewed (10,91). Instmmentation for photodynamic therapy has been reviewed (99). 

Functional dyes (1) of many types are important photochemical sensitizers for oxidation, polymerization, (polymer) degradation, isomerization, and photodynamic therapy. Often, dye stmctures from several classes of materials can fulfiH a similar technological need, and reviewing several dye stmctures... 

Natural Sensitizing Dyes and Photodynamic Therapy. The chlorophylls are, of course, among the natural sensitizers for photosynthesis. Considerable iaterest exists ia chlorophyll and related pigments as photosensitizers ia biology and medicine (75), isomeric retinal chromophores as visual pigments (76,77), and the use of synthetic photosensitizers ia neurobiology (9), hematology (78), and photodynamic therapy (79). 

Porphyrins, modified natural chlorophylls, chlorins, phthalocyanins, xanthenes, phenothiazine, and phenoxazine dyes as new sensitizers for photodynamic therapy 98MI50, 98MI51, 98MI52, 98MI53. 

Figure 2 Schematic of tumor phototherapy using a sensitizing drug (photodynamic therapy) (reproduced by permission of the Royal Society of Chemistry from Chem. Soc. Rev., 1995, 24, 19-33.)...

Misawa, J., Moriwaki, S.I., Kohno, E., Hirano, T., Tokura, Y., Takigawa, M. (2005) The role of low-density lipoprotein receptors in sensitivity to killing by Photofrin-mediated photodynamic therapy in cultured human tumor cell lines. J. Dermatol. Sci. July 20. 

Milanesio ME, Alvarez MG, Rivarola V, Silber JJ, Durantini EN (2005) Porphyrin-fullerene C60 dyads with high ability to form photoinduced charge-separated state as novel sensitizers for photodynamic therapy. Photochem Photobiol 81 891-897. 

Rancan F, Helmreich M, Molich A, JuxN, Hirsch A, Roder B, Witt C, Bohm F (2005) Fullerene-pyropheophorbide a complexes as sensitizer for photodynamic therapy uptake and photo-induced cytotoxicity on Jurkat cells. J Photochem Photobiol B 80 1-7. 

The obtained results have shown that cell cultures of tumor origin are more sensitive to phototoxic damage induced by solid-phase C60 than the cultures of nontumor origin (normal or spontaneously transformed ones) - the effect that could be interesting for the perspective of possible fullerene usage in photodynamic therapy of tumors. 

Many compounds sensitize biomolecules to damage by UVA (320-380 nm) and visible light. Two general mechanisms of sensitization are encountered. The Type I mechanism involves electron or hydrogen transfer from the target molecule to the photosensitizer in its triplet state. If 02 is present, this can be reduced to 02 by the reduced sensitizer. In the Type II mechanism, the excited sensitizer is quenched by 02, which is excited to the singlet state (typically A"g) and attacks the target molecule. Photosensitization is exploited in photodynamic therapy (PDT) for the destruction of cancerous or other unwanted cells. 

Functional dyes of many types are important photochemical sensitizers for chemical reactions involving oxidation, polymerization, (polymer) degradation. isomerization, and photodynamic therapy. Often, dye structures from several classes or materials can fulfill a similar technological need, particularly for laboratory or small-scale reactions where production efficiency may be of secondary importance. Commercial photochemical technology, however, is more selective and requires photochemical efficiency, ease of product separation, and lack of unwanted side reactions to an extent similar to that required by imaging processes. In addition, reusability of the spectral sensitizer is also preferred in commercial photochemical reactions. 

Absorption of a photon to produce a triplet excited state (via intersystem crossing from the first excited singlet state) can lead to energy transfer to another molecule. The phenomenon is used in photography for sensitization of the red end of the visible spectrum. More recent uses are in photodynamic therapy, an... 

Using similar methodology, 2,4,6-triarylselenopyrylium hexafluorophosphates were obtained and evaluated as in-vivo sensitizers for photodynamic therapy of cancer [226-229],... 

I Chen Z, Woodburn KW, Shi C, et al. Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells. Arterioscler 7hromb Vase Biol 2001 21 759-764. 

As shown in Fig. 7.6, texaphyrins have a larger cavity than porphyrins so they can form complexes with lanthanide metals such as gadolinium (XCYTRIN ), that enhances the efficacy of treatment for certain brain tumours, and lutetium (LUTRIN ), used as a sensitizer for photodynamic therapy of recurrent breast cancer [17], Crucial to their success is the increased number of donor atoms available as the more lanthanide binding sites that a ligand can satisfy, the more stable the complex. 

Photoimmunotoxins (sensitizers for photodynamic therapy of tumors) 93KFZ(10)7). 

Lang K, Mosinger J, Wagnerova DM. Photophysical properties of porphyrinoid sensitizers non-covalently bound to host molecules models for photodynamic therapy. Coord Chem Rev 2004 248 321-50. 

Figure 17.8 Two-photon photodynamic therapy (PDT) (a) simultaneous absorption of two near-infrared (NIP) photons raises the sensitizer to the S, excited state (b) sequential absorption of two photons, one from S0 and the other from T, raises the sensitizer to a higher excited state...

Drzewiecka A, Urbanska K, Matuszak Z, et al. Tritolylporphyrin dimer as a new potent hydrophobic sensitizer for photodynamic therapy of melanoma. Acta Biochim Pol 2001 48 277-82. 

Garbo GM. Purpurins and benzochlorins as sensitizers for photodynamic therapy. J Photochem Photobiol B Biol 1996 34 109-16. 

Gadolinium texaphyrin (Gd-tex Figure 4.8) is reported to be an effective radiation sensitizer for tumour cells, whilst the corresponding lutetium compound, which absorbs light in the far-red end of the visible spectrum, is in Phase II trials for photodynamic therapy for brain tumours and breast cancer. 

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