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Dual mode polyspermine with tunable degradability for plasmid DNA and siRNA delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
7986 572 2011 12 PDF Available
Title
Dual mode polyspermine with tunable degradability for plasmid DNA and siRNA delivery
Abstract

Stimuli-responsive degradability is an indispensable design component for polymeric gene carriers. In order to obtain enhanced, non-cytotoxic, and molecularly tunable nonviral gene delivery, spermine, a bioavailable small cationic molecule, was polymerized with diacrylate cross-linkers with or without acid-degradable ketal linkages for controlled dual mode-degradability (i.e., differential degradations in the endosome and the cytosol). The effects of ketal to ester ratios in the polymeric backbone on degradation rate, condensation of both plasmid DNA and siRNA, cellular uptake, intracellular disassembly, and consequent DNA transfection and RNA interference efficiency in vitro and in vivo were investigated. Limited nucleic acid complexation and cellular uptake but efficient intracellular release of nucleic acids were obtained with poly(spermine ketal ester) (PSKE), the most acid-degradable polyspermine. In contrast, poly(spermine ester) (PSE), which is not acid-degradable, demonstrated efficient nucleic acid complexation and cellular uptake but inefficient intracellular release of nucleic acids. The highest in vitro DNA transfection was obtained by the random co-polymer of PSKE and PSE at an equal ratio (PSKE-PSE), attributed to its balanced DNA complexation and acid-responsive release efficiency, while efficient siRNA unpackaging by PSKE resulted in the highest gene silencing efficiency. Preliminary in vivo studies demonstrated that the highest DNA transfection was obtained by using PSE, while both PSKE and PSE silenced GFP expression at the similar level. In conclusion, dual mode-degradable polyspermine is a non-cytotoxic nonviral gene carrier, and its acid-degradability can be molecularly tuned for differentially controlled transfection and gene silencing in vitro and in vivo.

Keywords
Polyspermine; Nonviral gene delivery; Biodegradability; DNA and siRNA delivery; In vitro and in vivo transfection; Intracellular release
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Dual mode polyspermine with tunable degradability for plasmid DNA and siRNA delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 16, June 2011, Pages 4009–4020
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