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Current Topics in Pharmacology   Volumes    Volume 8  Issue 2
Photodynamic therapy: selective uptake of photosensitizing drugs into tumor cells
Juan C. Stockert, Angeles Juarranz, Angeles Villanueva, Santi Nonell, Richard W. Horobin, Arnaldo T. Soltermann, Edgardo N. Durantini, Viviana Rivarola, Lucas L. Colombo, Jesús Espada, Magdalena Cañete
Pages: 185 - 217
Number of pages: 33
Current Topics in Pharmacology
Volume 8  Issue 2

Copyright © 2004 Research Trends. All rights reserved


The mechanisms of cell and tissue damage by photosensitization processes (e.g. photodynamic therapy (PDT) of cancer) constitute a subject of increasing interest in biomedical research. Singlet oxygen (1O2) and other highly reactive oxygen species are generated from the excited photosensitizer (PS) and represent the primary cytotoxic agents responsible for cell photo-killing. In addition to the hematoporphyrin-based drugs first used, second-generation PSs with improved photochemical and photobiological properties are now extensively studied in experimental models and clinical trials. New PS carriers and delivery procedures have also been developed to provide more selective targeting of tumoral tissues. Effective photodamage in both cell cultures and tumors is related to the chemical structure of each PS, as well as the concentration, incubation time, vehiculization procedure, light dose, and site of sub-cellular localization. Numerous cell components have been described as targets for the cytotoxic effects of 1O2, including mitochondria, lysosomes, Golgi apparatus, plasma membrane, and nuclei. Cytoskeletal structures (mainly microtubules and microfilaments) are also clearly affected by photosensitization. PSs localizing in mitochondria and lysosomes are highly effective for cell photodamage, triggering either apoptotic or necrotic cell death responses. Quantitative structure-activity relationships (QSAR) between physicochemical and biological characteristics of PSs are important in PDT research, and involve their solubility, 1O2 production, selective uptake into tumor cells, mechanisms of intracellular localization, and photokilling efficiency. Based on known chemical structure parameters and datasets concerning entry and localization of dyes and fluorescent probes into living cells, a QSAR approach to explain and predict selective accumulation of PSs within certain cell organelles is described.

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