Document Detail


Acid-degradable cationic methacrylamide polymerized in the presence of plasmid DNA as tunable non-viral gene carrier.
MedLine Citation:
PMID:  18585778     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
New acid-degradable cationic nanoparticles were synthesized using a monomer-to-polymer approach, which enabled highly flexible nanoparticle fabrication to obtain controlled properties such as size and conjugation with additional functionalities. The nanoparticles were designed to cause swelling and osmotic destabilization of the endosome, while cationic branches holding anionic DNA are cleaved from the polymeric backbone of the nanoparticles and make plasmid DNA accessible for efficient gene expression. Efficient release of plasmid DNA upon hydrolysis of the nanoparticles at the endosomal pH 5.0 and transportation of the released DNA to the nucleus of a cell were shown. In vitro studies showed significantly higher transfection efficiency by the degradable nanoparticles than polyethylenimine (PEI) polyplexes at very low concentrations (i.e., ng/mL). Size-dependent selective transfection of phagocytic cells (e.g., RAW 309 macrophages) and non-phagocytic cells (e.g., NIH 3T3 fibroblasts) was also achieved by using nanoparticles of two different sizes (240 nm and 680 nm in diameter), which implies feasibility of tunable gene therapy and DNA vaccination using the nanoparticle system. Preliminary pulmonary transfection of mice using the degradable nanoparticles demonstrated a remarkably higher expression of firefly luciferase at 70% lower concentration than using naked DNA alone. Implications and further improvement of the nanoparticles to be used in gene therapy are also discussed.
Authors:
In Kap Ko; Assem Ziady; Shiwei Lu; Young Jik Kwon
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-27
Journal Detail:
Title:  Biomaterials     Volume:  29     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-08-01     Completed Date:  2008-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  3872-81     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
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MeSH Terms
Descriptor/Qualifier:
Acrylamides / chemistry*,  metabolism
Animals
Cell Line
DNA / chemistry*
Gene Therapy / methods*
Gene Transfer Techniques*
Genetic Vectors / genetics,  metabolism*
Luciferases / genetics,  metabolism
Materials Testing
Mice
Molecular Structure
Particle Size
Plasmids / genetics*
Polymers / chemistry*,  metabolism
Transfection
Chemical
Reg. No./Substance:
0/Acrylamides; 0/Polymers; 79-39-0/methacrylamide; 9007-49-2/DNA; EC 1.13.12.-/Luciferases

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


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