Nanomedicine and Drug Delivery

0381465 - ÚMCH 2013 RIV CA eng M - Monography Chapter
Pola, Robert - Pechar, Michal - Ulbrich, Karel - Carlisle, R. C. - Willemsen, R. A. - Seymour, L. W.
Polymer-modified gene delivery vectors retargeted with recombinant proteins.
Nanomedicine and Drug Delivery. Volume 1. Oakville: Apple Academic Press, 2012 - (Sebastian, M.; Ninan, N.; Haghi, A.), s. 33-38. Advances in Nanoscience and Nanotechnology. ISBN 978-1-926895-17-8
R&D Projects: GA ČR GA203/08/0543; GA MŠMT 1M0505
Institutional research plan: CEZ:AV0Z40500505
Keywords : bungarotoxin * poly(ethylene glycol) * prostate-specific membrane antigen
Subject RIV: CD - Macromolecular Chemistry
http://www.appleacademicpress.com/title.php?id=9781926895178

We have prepared and characterized a multivalent reactive N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) bearing bungarotoxin-binding peptide (BTXbp). The polymer was used for covalent surface modification of adenoviral vectors containing luciferase reporter gene (Ad). The peptide BTXbp is known to have extremely high binding affinity to bungarotoxin (BTX) –a protein strongly binding to acetylcholine receptors. A recombinant protein consisting of antiPSMA antibody scFv fragment and BTX binding site (BTX-scFv) was used for retargeting of the polymer-modified Ad to prostate-specific membrane antigen (PSMA) receptors. While the polymer-modified Ad exhibited approximately 100-fold lower infectivity than the naked virus (in terms of luciferase expression), the addition of BTX-scFv to the polymer-coated Ad led to about 10-fold restoration of luciferase expression in PSMA-positive LNCaP cells. No such increase of transduction activity was observed in PSMA-negative PC3 cells. We have shown that the presented PHPMA-BTXbp/BTX-scFv system can be used as a universal tool for a receptor-specific viral gene therapy.
Permanent Link: http://hdl.handle.net/11104/0211927