Porphyrin‐related photosensitizers for cancer imaging and therapeutic applications

Journal of Microscopy - Tập 218 Số 2 - Trang 133-147 - 2005
Kristian Berg1, Pål Kristian Selbo1, Anette Weyergang1, Andreas Dietze1, Lina Prasmickaite1, Anette Bonsted1, Birgit Engesæter1, Even Angell‐Petersen2, Trond Warloe2, Niels Frandsen3, Anders Høgset4
1Department of Radiation Biology, and
2Department of Surgical Oncology, The Norwegian Radium Hospital, Oslo, Norway
3Santaris Pharma A/S, Bøge Allé 3, DK-2970 Hørsholm, Denmark
4PCI Biotech AS, Hoffsveien 48, N-0377, Oslo, Norway

Tóm tắt

SummaryA photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5‐aminolevulinic acid (5‐ALA) or 5‐ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosenisitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome‐inactivating proteins, immunotoxins, gene‐encoding plasmids, adenovirus, peptide‐nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.

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Journal of Microscopy

Tập 218 Số 2

133-147

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