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Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
8613 599 2011 10 PDF Available
Title
Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles
Abstract

A reduction-sensitive linear cationic click polymer (RCP) was specially designed for the efficient gene delivery to overcome multidrug resistance (MDR) by RNA interference to silence the expression of P-glycoprotein (P-gp). RCP was synthesized via the “click chemistry” with disulfide bonds, amide–triazole moieties and secondary amine groups in the main chain. RCP could efficiently condense pDNA into nanoparticles (RCPNs) around 150 nm. Polyplex dissociation was observed in the presence of 2.5 mm DTT due to the cleavage of disulfide bonds, which indicated the efficient DNA release under the reduction condition. In vitro transfection and cytotoxicity experiments against human breast cancer MCF-7 cells and drug-resistant MCF-7/ADR cells showed that RCPNs could bring about higher transfection efficiency with much lower cytotoxicity than PEI/DNA nanoparticles. RCPNs loaded with plasmid iMDR1-pDNA could inhibit P-gp expression, increase adriamycin (ADR) accumulation and enhance cytotoxicity of ADR against MCF-7/ADR cells. Combination of RCPNs and ADR could suppress the tumor growth more efficiently than using ADR only on mouse xenograft model bearing ADR resistant human breast cancer. These results suggested that this RCP could be a potential, safe and efficient non-viral vector for reversing MDR.

Keywords
Click chemistry; RNA interference; Disulfide bond; P-glycoprotein; Multidrug resistance
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Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 6, February 2011, Pages 1738–1747
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