Cationic liposomes as delivery systems for double-stranded PNA-DNA chimeras exhibiting decoy activity against NF-kappaB transcription factors.
Peptide nucleic acids (PNAs) have been recently proposed as useful molecules in pharmacogenetic therapy, especially due to the fact that they show a very high stability with respect to DNA and RNA. However, PNAs are not efficient decoy molecules, are characterized by negligible cell internalization and low solubility and are not suitable to be delivered by liposomes. With respect to the biological activity of PNA-based molecules, PDP deserve great consideration, due to the fact that they exhibit high levels of solubility, and are expected to be resistant to proteinases and exonucleases. In this manuscript we determined whether double-stranded molecules based on PNA-DNA chimeras containing NF-kappaB binding sites, exhibit decoy activity against NF-kappaB transcription factors. In addition, we determined whether they can be complexed by cationic liposomes. The results obtained demonstrated that hybrids based on PNA-DNA chimeras are powerful decoy molecules against NF-kappaB p52 transcription factor. In addition, we found that cationic liposomes can be proposed for in vitro delivery to target cells of these decoy molecules. The results presented in this paper are thus of practical importance, since the simplicity and the versatility of the cationic liposome technology have made cationic liposomes useful nonviral gene delivery systems for human gene therapy.
Borgatti
Monica
M
Department of Biochemistry and Molecular Biology, University of Ferrara, Via Luigi Borsari 46, Italy.
Breda
Laura
L
Cortesi
Rita
R
Nastruzzi
Claudio
C
Romanelli
Alessandra
A
Saviano
Michele
M
Bianchi
Nicoletta
N
Mischiati
Carlo
C
Pedone
Carlo
C
Gambari
Roberto
R
D001665:Binding Sites; D002412:Cations / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D020014:K562 Cells; D008081:Liposomes; D018716:Molecular Mimicry; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D002412:Cations; D008081:Liposomes; D016328:NF-kappa B; D020135:Peptide Nucleic Acids; D004247:DNA