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Mono-methoxy-poly(3-hydroxybutyrate-co-4-hydroxybutyrate)-graft-hyper-branched polyethylenimine copolymers for siRNA delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
7474 553 2012 11 PDF Available
Title
Mono-methoxy-poly(3-hydroxybutyrate-co-4-hydroxybutyrate)-graft-hyper-branched polyethylenimine copolymers for siRNA delivery
Abstract

A class of non-viral siRNA vectors consisting of biodegradable poly(hydroxyalkanoates) (PHA) grafted onto branched poly(ethyleneimine) (bPEI, 25 kDa) was synthesized and evaluated for siRNA delivery. The mPHA-g-bPEI copolymers were synthesized through Michael addition between acrylated mono-methoxy-poly(hydroxyalkanoates) (mPHA-acrylated) and bPEI with various block length poly(hydroxyalkanoates) from 1300 to 2900 Da. Our research showed that mPHA-g-bPEI copolymers could effectively bind siRNA, protect it from degradation by nucleases and efficiently release the complexed siRNA in the presence of low concentrations of polyanionic heparin. The particle size of mPHA-g-bPEI/siRNA complexes was <200 nm with ζ-potential between 33 and 43 mV. mPHA-g-bPEI copolymers displayed low cytotoxicity compared to unmodified bPEI and efficient cellular uptake of Cy3-siRNA in A549 cells by flow cytometry and confocal microscopy. siRNA delivery efficiency of the copolymers was assessed by siRNA against luciferase in cultured A549-Luc and MCF-7-Luc cells. Those mPHA-g-bPEI copolymers revealed a higher transfection efficiency and lower cytotoxicity than bPEI in two cell lines. Furthermore, a remarkable knockdown of luciferase expression of mPHA-g-bPEI (mAP2) complex (up to 85%) in vitro was found to be equivalent to that of commercially available transfection agent Lipofectamine™ 2000.

Keywords
siRNA delivery; Poly(hydroxyalkanoates); Poly(ethyleneimine); Non-viral vector
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Mono-methoxy-poly(3-hydroxybutyrate-co-4-hydroxybutyrate)-graft-hyper-branched polyethylenimine copolymers for siRNA delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 7, March 2012, Pages 2334–2344
Authors
, , , , , ,
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