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Polymer probes for photodynamic therapy of solid tumors
Kotalík, Kevin ; Etrych, Tomáš (advisor) ; Kovář, Marek (referee)
One of the currently studied promising strategies in advanced oncologic treatment is photodynamic therapy, a method based on the administration of so-called photosensitisers, i.e. photoactive compounds such as porphyrins, and subsequent irradiation of tumor tissue with light of appropriate wavelength. An excitation of the photosensitiser, present in the tumor area, is hence invoked and reactive oxygen species (ROS) are formed. These species afterward cause the apoptosis of the tumor cells, leading to destruction of tumor tissue. In photodynamic therapy, the strategy of administration of a prodrug which is metabolised to the active photosensitiser can be used with advantages. In photodynamic therapy, this prodrug may be 5-aminolevulinic acid (5-ALA) or its esters which are metabolised to protoporphyrin IX (PPIX), the photosensitiser proper. The targeted drug delivery to the tumor tissue can be achieved by using various delivery systems, e.g. water-soluble polymer conjugates carrying the drug. Due to their size, these polymer conjugates are accumulated in solid tumors on the basis of the enhanced permeability and retention (EPR) effect. Macromolecules can penetrate the tumor vasculature, which, unlike that of healthy tissue, is imperfectly developed and contains gaps between endothelial cells....
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