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Cationic core–shell liponanoparticles for ocular gene delivery

Paper ID Volume ID Publish Year Pages File Format Full-Text
6668 510 2012 10 PDF Available
Title
Cationic core–shell liponanoparticles for ocular gene delivery
Abstract

To achieve enhanced gene transfection efficiency with ocular eye-drop therapy, a cationic core–shell liponanoparticle (DLCS-NP) was designed by enveloping the plasmid-laden chitosan nanoparticle (CS-NP) into a cationic lipid shell. The cellular uptake of DLCS-NP was up to 1.25-fold and 5-fold higher than that of CS-NP and lipid-coated chitosan nanoparticles (LCS-NP), respectively. Further endocytosis inhibition investigation discovered that facilitated by the cationic outer lipid layer, several other distinct pathways (besides clathrin-mediated endocytosis) were involved in the endocytosis of DLCS-NP. Endolysosome trafficking experiment verified that cationic lipid coating could facilitate the endolysosome escape of DLCS-NP. Consequently, using enhanced green fluorescence protein (EGFP) as a reporter gene, DLCS-NP-treated human conjunctival epithelial cells exhibited 3.1- and 3.5-fold more intense EGFP expression than that of LCS-NP and CS-NP, respectively. Finally, in vivo transfection experiments on rabbits revealed that EGFP expression exhibited 2.52-fold increase in DLCS-NP group than that of CS-NP group. In summary, this type of cationic core–shell liponanoparticle, possessing multiple functions including better DNA protecting effect, superior cellular uptake efficiency, utilization of multiple endocytic pathways, and endolysosome escaping ability, may represent a promising strategy for ocular gene delivery.

Keywords
Core–shell; Cationic lipids; Chitosan nanoparticles; Endocytosis pathway; Lysosome; Transfection
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 30, October 2012, Pages 7621–7630
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