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Target specific tumor treatment by VEGF siRNA complexed with reducible polyethyleneimine–hyaluronic acid conjugate

Paper ID Volume ID Publish Year Pages File Format Full-Text
8389 588 2010 8 PDF Available
Title
Target specific tumor treatment by VEGF siRNA complexed with reducible polyethyleneimine–hyaluronic acid conjugate
Abstract

Target specific delivery of small interfering RNA (siRNA) has been regarded as one of the most important technologies for the development of siRNA therapeutics. In this work, non-toxic low molecular weight (MW) polyethyleneimine (PEI, 2000 Da) was cross-linked with cystamine bisacrylamide (CBA) to prepare reducible PEI-SS in the body. Then, PEI-SS was conjugated with hyaluronic acid (HA) in the form of block-copolymer to enhance serum stability and facilitate target specific cellular uptake of siRNA by HA receptor mediated endocytosis. The cytotoxicity of (PEI-SS)-b-HA conjugate appeared to be negligible likely due to the degradation of PEI-SS to low MW PEI in the cytosol. Flow cytometric and confocal microscopic analyses confirmed the HA receptor mediated endocytosis of siRNA/(PEI-SS)-b-HA complex. The siRNA/(PEI-SS)-b-HA complex demonstrated an excellent in vitro gene silencing efficiency in the range of 50–80% reducing the mRNA expression level in the absence and presence of 50 vol% serum. Moreover, intra-tumoral injection of vascular endothelial growth factor (VEGF) siRNA/(PEI-SS)-b-HA complex resulted in dramatically inhibited tumor growth with reduced VEGF mRNA and VEGF levels in the tumors.

Keywords
Hyaluronic acid; Polyethyleneimine; siRNA; Target delivery; Gene silencing
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Target specific tumor treatment by VEGF siRNA complexed with reducible polyethyleneimine–hyaluronic acid conjugate
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 19, July 2010, Pages 5258–5265
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