Document Detail


Complexation to cationic microspheres of double-stranded peptide nucleic acid-DNA chimeras exhibiting decoy activity.
MedLine Citation:
PMID:  15316146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The major aim of this paper was to determine whether cationic microspheres (CM), consisting of the permeable polymer Eudragit RS 100 plus the cationic surfactant dioctadecyl-dimethyl-ammonium bromide (DDAB(18)), could bind to double-stranded peptide nucleic acid PNA-DNA-PNA (PDP) chimeras exhibiting decoy activity against NF-kappaB transcription factors. Microspheres were produced by the 'solvent evaporation method' and centrifugation at 500, 1,000 and 3,000 rpm to obtain different-sized microparticles. Microsphere morphology, size and size distribution were determined by optical and electron microscopy observations. In order to determine their binding activity, double-stranded DNA-based and PDP-based decoy molecules were incubated with different amounts of microparticles in the presence of 100 ng of either (32)P-labeled DNA-DNA or DNA-PDP hybrid molecules or cold PDP-PDP hybrids. The complexes were analyzed by agarose gel electrophoresis. The resistance of (32)P-labeled DNA-DNA and DNA-PDP molecules in the presence of serum or cellular extracts was evaluated after binding to CM by gel electrophoresis analysis. DDAB(18) Eudragit RS 100 microspheres are able to bind to DNA-PDP and PDP-PDP hybrids, to deliver these molecules to target cells and to protect DNA-PDP molecules from enzymatic degradation in simulated biological fluids. In addition, when assayed in ex vivo conditions, DDAB(18) Eudragit RS 100 microspheres exhibited low toxicity. The results presented in this paper demonstrate that CM can be considered suitable formulations for pharmacogenomic therapy employing double-stranded PDP chimeras.
Authors:
Carlo Mischiati; Alessia Sereni; Alessia Finotti; Laura Breda; Rita Cortesi; Claudio Nastruzzi; Alessandra Romanelli; Michele Saviano; Nicoletta Bianchi; Carlo Pedone; Monica Borgatti; Roberto Gambari
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of biomedical science     Volume:  11     ISSN:  1021-7770     ISO Abbreviation:  J. Biomed. Sci.     Publication Date:    2004 Sep-Oct
Date Detail:
Created Date:  2004-08-18     Completed Date:  2005-01-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421567     Medline TA:  J Biomed Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  697-704     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Binding Sites
Chimera*
DNA / chemistry*,  genetics
Humans
K562 Cells
Microspheres*
Oligodeoxyribonucleotides
Peptide Nucleic Acids / chemistry*
Solvents
Transcription Factors / metabolism
Chemical
Reg. No./Substance:
0/Oligodeoxyribonucleotides; 0/Peptide Nucleic Acids; 0/Solvents; 0/Transcription Factors; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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