TY - THES T1 - New therapeutic options for the treatment of lung cancer by telomerase inhibition A1 - Tätz,Sebastian Y1 - 2009/04/02 N2 - The enzyme telomerase plays an important role in cell immortalization and hence cancer development. It can be detected in most kinds of tumors but is not expressed in the majority of healthy cells. Therefore, telomerase inhibition appears to be a promising approach for a specific cancer therapy with reduced side effects. The work presented here concentrated on the treatment of non-small cell lung cancer by telomerase inhibition and can be divided into three parts: 1. Characterization of the G-quadruplex stabilizing substance BRACO19 under biopharmaceutical and stability aspects. BRACO19 showed a poor permeability across biological barriers and was instable under physiological conditions. 2. Evaluation of cationic chitosan/PLGA nanoparticles as a carrier system for 2';-O-Methyl-RNA antisense oligonucleotides (2OMR), which was directed against the template region of the telomerase specific RNA hTR. The chitosan content in the particles considerably influenced the uptake improvement of 2OMR into cells. Despite a poor complex stability in physiological media a successful inhibition of telomerase activity in lung cancer cells could be achieved. 3. Targeted delivery of anti-telomerase siRNA to CD44-overexpressing lung cancer cells using hyaluronic acid modified DOTAP/DOPE liposomes. These liposomes efficiently bound siRNA, protected it from degradation by nucleases and increased its uptake into CD44-overexpressing lung cancer cells. The modification improved the colloidal stability of lipoplexes in cell culture medium and their cytotoxicity. KW - Lungenkrebs KW - Telomerase KW - Telomer KW - Nanopartikel KW - Liposom KW - Lipoplexe KW - Antisense-Oligonucleotide KW - Antisense-RNS CY - Saarbrücken PB - Universitäts- und Landesbibliothek AD - Postfach 151141, 66041 Saarbrücken UR - http://scidok.sulb.uni-saarland.de/volltexte/2009/2122 ER -