AS1411 is a G-rich DNA oligonucleotide that functions as an aptamer of the protein nucleolin, found at high levels on the surface of cancer cells but not on the surface of normal cells. Herein, we have studied AS1411 as a supramolecular carrier for the delivery of an acridine-based G-quadruplex ligand, C8, to HeLa cancer cells. Two AS1411 derivatives, LNA-AS1411 and U-AS1411, were also tested, in an attempt to compare AS1411 pharmacological properties. The results showed that AS1411-C8 complexation was made with great binding strength and that it lowered the ligand's cytotoxicity towards non-malignant cells. This effect was suggested to be due to a decreased internalization of the complexed versus free C8 as shown by flow cytometry. The AS1411 derivatives, despite forming a stable complex with C8, lacked the necessary tumour-selective behaviour. The binding of C8 to AS1411 G-quadruplex structure did not negatively affect the recognition of nucleolin by the aptamer. The AS1411-C8 repressed c-MYC expression at the transcriptional level, possibly due to C8 ability to stabilize the c-MYC promoter G-quadruplexes. Overall, this study demonstrates the usefulness of AS1411 as a supramolecular carrier of the G-quadruplex binder C8 and the potential of using its tumour-selective properties for the delivery of ligands for cancer therapy.

• MeSH
• aptamery nukleotidové metabolismus   farmakologie   MeSH
• buněčné linie MeSH
• buňky A549 MeSH
• fibroblasty cytologie   účinky léků   metabolismus   MeSH
• fosfoproteiny antagonisté a inhibitory   genetika   metabolismus   MeSH
• G-kvadruplexy * MeSH
• genetická transkripce MeSH
• HeLa buňky MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nukleolin MeSH
• oligodeoxyribonukleotidy metabolismus   farmakologie   MeSH
• orgánová specificita MeSH
• promotorové oblasti (genetika) MeSH
• proteiny vázající RNA antagonisté a inhibitory   genetika   metabolismus   MeSH
• protinádorové látky metabolismus   farmakologie   MeSH
• protoonkogenní proteiny c-myc genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• technika přenosu genů MeSH
• vazba proteinů MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AGRO 100 MeSH Prohlížeč
• aptamery nukleotidové MeSH
• fosfoproteiny MeSH
• ligandy MeSH
• oligodeoxyribonukleotidy MeSH
• proteiny vázající RNA MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny c-myc MeSH