Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-9-12
pubmed:abstractText
A novel cytoplasmic delivery system of antisense oligodeoxynucleotide (asODN) was developed by assembling a PEG-asODN conjugate with disulfide linkage (smart linkage) (PEG-SS-asODN) into polyion complex (PIC) micelles through the complexation with branched poly(ethylenimine) (B-PEI). The PIC micelle thus prepared showed a significant antisense effect against luciferase gene expression in HuH-7 cells, far more efficient than nonmicelle systems (asODN and PEG-SS-asODN in free form) and PIC micelle encapsulating the conjugate without the disulfide linkage. Use of poly(l-lysine) (PLL) instead of the B-PEI for PIC micellization led to a substantial decrease in the antisense effect. These results indicate that the PIC micelles formulated from PEG-SS-asODN conjugate and B-PEI is successfully transported from the endosomal compartment into the cytoplasm by the buffering effect of the B-PEI, releasing hundreds of active asODN molecules via cleavage of the disulfide linkage into the cellular interior, responding to a high glutathione concentration in the cytoplasmic compartment. Furthermore, the type of smart linkage (glutathione-sensitive SS linkage vs pH-sensitive linkage) in the conjugates substantially affected the antisense effect of the PIC micelles, depending on the nature of the counter polycation (B-PEI vs PLL).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1525-7797
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2449-54
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16153078-Biocompatible Materials, pubmed-meshheading:16153078-Carcinoma, Hepatocellular, pubmed-meshheading:16153078-Cations, pubmed-meshheading:16153078-Cell Line, Tumor, pubmed-meshheading:16153078-Chromatography, pubmed-meshheading:16153078-Cytoplasm, pubmed-meshheading:16153078-Disulfides, pubmed-meshheading:16153078-Genes, Reporter, pubmed-meshheading:16153078-Humans, pubmed-meshheading:16153078-Hydrogen-Ion Concentration, pubmed-meshheading:16153078-Ions, pubmed-meshheading:16153078-Luciferases, pubmed-meshheading:16153078-Micelles, pubmed-meshheading:16153078-Models, Biological, pubmed-meshheading:16153078-Models, Chemical, pubmed-meshheading:16153078-Oligonucleotides, Antisense, pubmed-meshheading:16153078-Polyethylene Glycols, pubmed-meshheading:16153078-Polylysine
pubmed:articleTitle
Supramolecular assemblies for the cytoplasmic delivery of antisense oligodeoxynucleotide: polyion complex (PIC) micelles based on poly(ethylene glycol)-SS-oligodeoxynucleotide conjugate.
pubmed:affiliation
Tsukuba Research Center for Interdisciplinary Materials Science (TIMS), University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8573, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't