TY  - THES
T1  - New models for telomerase inhibition by antisense 2'-O-methyl-RNA in lung cancer therapy
A1  - Dong,Meng
Y1  - 2011/05/12
N2  - Telomerase activity can be detected in about 80% of non-small cell lung cancers (NSCLC). Inhibition of telomerase is a specific approach for treatment of NSCLC. The oligonucleotide 2'-O-methyl-RNA (OMR) binding to the RNA component of telomerase acts as a selective telomerase inhibitor. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles which are capable to form nanoplexes with OMR are one promising carrier system for OMR delivery. This thesis is mainly focused on the therapeutic potential of OMR based on different in vitro and ex vivo models. In cell culture models, delivery of OMR by nanoparticles exhibited 50%-70% telomerase inhibition 72h after treatment. In A549 cells telomerase activity was continuously reduced by 80% and the telomere length shortened about 50% during a treatment for 102 days with nanoplexes. In a new tissue slice model, nanoplexes can penetrate into tumor tissue slices, deliver OMR and subsequently inhibit telomerase activity by about 40% without changing tissue architecture. An isolated perfused rat lung model was successfully applied to investigate the inhalative delivery of nanoplexes to the lung without altering lung physiology. In 40 NSCLC tumor samples, stem cell marker CD133 positive tumor cells tend to have a lower telomerase activity. These experiments provide evidence that telomerase inhibitors delivered by nanoparticles have a great potential for in vivo application to render a more selective anticancer therapy.
KW  - Lungenkrebs
KW  - Telomerase
KW  - Nanopartikel
KW  - Antisense-Oligonucleotide
KW  - Inhibition
KW  - Telomer <Molekulargenetik>
KW  - Inhalation
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2011/3930
ER  -