Based Photosensitizers

Porphyrin-based photosensitizers for use in photodynamic therapy 98T4151. 

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. 

Based on optimized conditions, complete inactivation of influenza vims is achieved in allantoic fluid (resulting in a decrease in the infectious titer of the vims from >4-5 log10 EID50 to 0) using separable fullerene-based photosensitizer. 

Novel porphyrin-based photosensitizers, bacteriochlorins exhibiting long-wavelength absorptions between 788 and 831 nm, are promising candidates for... 

Most photosensitizers, however, are reasonably photostable compounds, and their optical properties have been studied in depth. In particular, there has been much interest in ruthenium-based photosensitizers such as [Ru(bpy)3]2+ and [Ru(phen)3]2+, due to their stability and absorption of visible light. Detailed information on their optical properties, including ground and excited state information in relation to photosensitization, has been reviewed by Creutz et al. [16]. Similarly, the photochemistry and photophysics of rhenium complexes, as discussed here, have been reviewed in detail by Kirgan et al. [7]. 

Nishiyama N, Amida JWD et al (2006) Photochemical enhancement of transgene expression by polymeric micelles incorporating plasmid DNA and dendrimer-based photosensitizer. J Drug Target 14 413 124... 

Sternberg, E.D. and Dolphin, D. (1998) Porphyrin-based Photosensitizers for Use in Photodynamic Therapy, Tetrahedron 54, 4151-4202. 

Sternberg ED, Dolphin D. Porphyrin-based photosensitizers for use in photodynamic therapy. Tetrahedron 1998 54 4151-202. 

DESIGN OF PORPHYRIN-BASED PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY... 

Another concern specific to the use of porphyrin-based photosensitizers is the fact that singlet state lifetimes are usually less than 10 ns and photosensitization occurs mostly from the triplet state. This requires the selection of systems that efficiently generate triplet states, which is not the case of paramagnetic metalloporphyrins. 

Guidelines to Design Better Porphyrin-Based Photosensitizers for PDT... 

In summary, these studies into the working mechanisms of PDT at a cellular level have shown that (a) PDT with mitochondria-based photosensitizers can induce extremely rapid apoptosis, (b) it can bypass some of the normal control mechanisms, such as bcl-2 and (c) although PDT induced apoptosis is dependent on p53 status, overall cell killing is not, which is of importance since many human tumors have non-functional p53. The majority of these studies have been performed in vitro and further studies should indicate whether the same responses occur in vivo. In addition, the role of apoptosis in the overall tumor response is not clear and recent data, using cell lines deficient in apoptotic machinery, indicate that these cells are still sensitive to PDT, probably by using a necrotic pathway [134]. This sensitivity could possibly be used in the treatment of tumors which are chemoresistant, and indeed several studies have already shown the effective use of PDT in this area [84,85,88,156]. 

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