Document Detail

Stabilizing effect of tyrosine trimers on pDNA and siRNA polyplexes.
MedLine Citation:
PMID:  23199743     Owner:  NLM     Status:  Publisher    
Nine sequence-defined, polycationic oligomers were synthesized containing motifs of three consecutive tyrosines (Y3) as stabilizing components for pDNA and siRNA polyplex assembly. For pDNA, a combination of terminal oligotyrosines and cysteines was necessary and sufficient for stable polyplex formation. Stable siRNA binding required a combination of terminal cysteines and oligotyrosines, as well as a central hydrophobic modification (oligotyrosines or fatty acids). The phenolic group within the aromatic amino acids of Y3 containing oligomers further increased the endosomal buffer capacity. As a result, the new class of oligotyrosine containing oligomers was efficient in pDNA and siRNA transfection, in most cases superior to a previously established cysteine-containing, dioleic acid modified oligomer without the Y3 motif. Additionally, increased serum stability of the new oligomers with terminal Y3 motifs was demonstrated by gel shift and fluorescence correlations spectroscopy (FCS). In vivo stability and biodistribution was monitored by intravenous administration of chemically stabilized Cy7 siRNA either as free form, or complexed with the nine Y3 containing oligomers or control oligomers. Oligomer 332, with the overall most beneficial in vitro and in vivo characteristics, was applied in RAN siRNA polyplexes for intratumoral treatment of neuroblastoma-bearing mice. This resulted in significantly reduced tumor growth compared to animal treated with control siRNA polyplexes.
Christina Troiber; Daniel Edinger; Petra Kos; Laura Schreiner; Raphaela Kläger; Annika Herrmann; Ernst Wagner
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-28
Journal Detail:
Title:  Biomaterials     Volume:  -     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Department of Pharmacy, Pharmaceutical Biotechnology, Center for System-based Drug Research and Center for NanoScience (CeNS), Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany.
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