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Acid-degradable cationic methacrylamide polymerized in the presence of plasmid DNA as tunable non-viral gene carrier

Paper ID Volume ID Publish Year Pages File Format Full-Text
9884 651 2008 10 PDF Available
Title
Acid-degradable cationic methacrylamide polymerized in the presence of plasmid DNA as tunable non-viral gene carrier
Abstract

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.

Keywords
Controlled drug release; Drug delivery; Gene transfer; Nanoparticles
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Acid-degradable cationic methacrylamide polymerized in the presence of plasmid DNA as tunable non-viral gene carrier
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 28, October 2008, Pages 3872–3881
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us