Novel nanostructural photosensitizers for photodynamic therapy
|Kinga Tataruch 1, Aleksandra Rusin 2, Mariusz Kępczyński 3, Zdzisław Krawczyk 2, Maria Nowakowska 3|
1. Cracow University of Economics, Faculty of Commodity Science, Rakowicka 27, Kraków 31-510, Poland
Photodynamic therapy is currently used as a popular form of photochemotherapy for a wide variety of clinical applications. This treatment requires the presence of a drug, called photosensitizer, activating light of a specific wavelength and molecular oxygen to produce a localized damage in tumor tissues and/or their vasculature. Many efforts have been undertaken to develop new agents with a high efficacy for photodynamic treatment of cancer and some other diseases. Porphyrins and their derivatives are studied as potential sensitizers because of their high anti-cancer efficiency. The factors limiting the use of porphyrins in PDT are their poor solubility in water, low chemical purity and high dark toxicity .
This paper presents the results of our studies on the development of the efficient nanoformulations of porphyrin for PDT. In the first step three PEG-functionalized porphyrins (p-THPP-PEG350, p-THPP-PEG2000 and p-THPP-PEG5000) were synthesized by covalent attachment of PEG chains of various molecular weights (350, 2000 and 5000 Da) to commercially available 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP). To improve their ability to penetrate the hydrophobic cell membrane, the conjugates were solubilized in liposome vesicles.
The usefulness of novel hybrid systems as photosensitizers in photodynamic therapy was tested in vitro. Dark and photo cytotoxicity of these photosensitizers delivered in solution or embedded in liposomes were evaluated on two cell lines: HCT 116 and DU 145 and compared with these treated with free p-THPP. The kinetics of cellular uptake and the intracellular co-localization of p-THPP-PEG2000 formulations (which exhibit the most significant photodynamic activity) were studied by means of flow cytometric analysis and confocal laser scanning microscopy with the application of properly chosen fluorescence markers. Additionally, the time course and the mechanism of cell death after PDT were determined .
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Presentation: Poster at Nano-Biotechnologia PL, by Kinga Tataruch
See On-line Journal of Nano-Biotechnologia PL
Submitted: 2012-06-29 15:03 Revised: 2012-06-29 15:03
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