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Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium

Paper ID Volume ID Publish Year Pages File Format Full-Text
8064 575 2010 7 PDF Available
Title
Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium
Abstract

A cardiomyocyte-targeted Fas siRNA delivery system was developed using primary cardiomyocyte (PCM) specific peptide-modified polymers with high transfection efficiency and low cytotoxicity. Primary cardiomyocyte (PCM) specific peptide, selected by phage display, was conjugated to bioreducible poly(cystamine bisacrylamide-diaminohexane, CBA-DAH) (PCD). The specificity of the PCM-modified polymer to cardiomyocytes was confirmed by competition study with free PCM ligand and by delivery to non-cardiomyocyte NIH 3T3 fibroblasts. The cellular binding and uptake of the PCM-polymer/pDNA polyplex was inhibited by addition of free PCM peptide. The impact of PCM conjugation on cellular uptake and transfection efficiency was greater in H9C2 rat cardiomyocytes than in NIH 3T3 cells. Fas siRNA/PCM-polymer polyplexes exhibited significant Fas gene silencing in rat cardiomyocytes under hypoxic conditions, leading to inhibition of cardiomyocyte apoptosis. These findings demonstrate the utility of the addition of a primary cardiomyocyte (PCM) specific peptide modification to a bioreducible polymer for targeted delivery of Fas siRNA to inhibit cardiomyocyte apoptosis.

Keywords
Cardiomyocyte; siRNA; Fas; PCM; Bioreducible polymer
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Primary cardiomyocyte-targeted bioreducible polymer for efficient gene delivery to the myocardium
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 31, November 2010, Pages 8081–8087
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