Photodynamic therapy (PDT) is a minimally invasive therapeutic modality used for the management of a variety of cancers and benign diseases. The destruction of unwanted cells and tissues in PDT is achieved by the use of visible or near-infrared radiation to activate a light-absorbing compound (a photosensitizer, PS), which, in the presence of molecular oxygen, leads to the production of singlet oxygen and other reactive oxygen species. These cytotoxic species damage and kill target cells. The development of new PSs with properties optimized for PDT applications is crucial for the improvement of the therapeutic outcome. This review outlines the principles of PDT and discusses the relationship between the structure and physicochemical properties of a PS, its cellular uptake and subcellular localization, and its effect on PDT outcome and efficacy.
1 September 1998 in Journal of Biological Chemistry
The ortho, meta, andpara isomers of manganese(III) 5,10,15,20-tetrakis(N-methylpyridyl)porphyrin, MnTM-2-PyP5+, MnTM-3-PyP5+, and MnTM-4-PyP5+, respectively, were analyzed in terms of their superoxide dismutase (SOD) activity in vitro and in vivo. The impact of their interaction with DNA and RNA on the SOD activity in vivo and in vitro has also been analyzed. Differences in their behavior are due to the combined steric and electrostatic factors. In vitro catalytic activities are closely related to their redox potentials. The half-wave potentials (E½) are +0.220 mV, +0.052 mV, and +0.060 Vversus normal hydrogen electrode, whereas the rates of dismutation (kcat) are 6.0 × 107, 4.1 × 106, and 3.8 × 106 m −1 s−1 for theortho, meta, and para isomers, respectively. However, the in vitro activity is not a sufficient predictor of in vivo efficacy. The ortho andmeta isomers, although of significantly different in vitro SOD activities, have fairly close in vivo SOD efficacy due to their similarly weak interactions with DNA. In contrast, due to a higher degree of interaction with DNA, thepara isomer inhibited growth of SOD-deficientEscherichia coli.